Source: UNIVERSITY OF CALIFORNIA, DAVIS submitted to NRP
CHEMISTRY OF LIPIDS IN FOODS AND TISSUES
Sponsoring Institution
National Institute of Food and Agriculture
Project Status
COMPLETE
Funding Source
HATCH
Reporting Frequency
Annual
Accession No.
0134682
Grant No.
(N/A)
Cumulative Award Amt.
(N/A)
Proposal No.
(N/A)
Multistate No.
(N/A)
Project Start Date
Oct 1, 2012
Project End Date
Sep 30, 2017
Grant Year
(N/A)
Program Code
[(N/A)]- (N/A)
Recipient Organization
UNIVERSITY OF CALIFORNIA, DAVIS
410 MRAK HALL
DAVIS,CA 95616-8671
Performing Department
Food Science and Technology
Non Technical Summary
The lipids are important to the quality, stability, safety and nutritional value of foods and beverages. The objectives of the research program are to describe the chemical, structural and biochemical properties of food lipids in molecular detail, at the nanometer and micrometer length scales using human milk as a biological model and to determine how these properties relate to the organoleptic, structural and nutritional value of foods. The goal is to define those molecules and structures of dietary fats that influence lipid metabolism in humans with sufficient accuracy to guide the composition of human foods to improve their effects on individual health.
Animal Health Component
(N/A)
Research Effort Categories
Basic
(N/A)
Applied
(N/A)
Developmental
(N/A)
Classification

Knowledge Area (KA)Subject of Investigation (SOI)Field of Science (FOS)Percent
3043420200010%
3043430200010%
5023420200020%
7013430100020%
7023450101020%
7011852100010%
7021852101010%
Knowledge Area
702 - Requirements and Function of Nutrients and Other Food Components; 304 - Animal Genome; 502 - New and Improved Food Products; 701 - Nutrient Composition of Food;

Subject Of Investigation
3430 - Cheese; 3420 - Butter; 1852 - Rape; 3450 - Milk;

Field Of Science
1010 - Nutrition and metabolism; 1000 - Biochemistry and biophysics; 2000 - Chemistry;
Goals / Objectives
The class of molecules termed lipids are vital to the quality, structures, stability, safety and nutritional value of foods and beverages. The goals of this project are to understand how different fats consumed in diets contribute to human health and thus how the compositions of commodities should be controlled as genetic traits to improve their overall value. Current dietary guidelines recommend that consumers limit the consumption of dietary fat yet there is little evidence on which to base specific compositions nor quantities as foods. Mammalian milks provide a model of how diet can influence many aspects of metabolism to understand which components in the diet act on which metabolic targets and how. Human milk contains a remarkable group of lipids in distinct structures. These molecules provide unique nutritional values, and the immediate goals are to understand which structures are responsible. Once the structures are known, we shall pursue methods to industrialize their production. OBJECTIVES: 1 Determine the role of fats and oils in the physical properties of foods. 2. Determine the role of fat composition, catalysts and inhibitors on the oxidative stability of foods. 3. Investigate the role of lipids in modifying food safety. 4. Investigate the role of lipids in the nutritional and health values of foods. The outcomes of these studies will form the basis for guidance for formulating foods for particular health targets based upon the metabolic sensitivity to dietary lipids.
Project Methods
The project will develop and refine methods and technologies to the compositions, structures, stability and nutritional value of lipids in foods. The molecular and colloidal structures of lipids will be defined by NMR, Raman spectroscopy and light scattering methods to build knowledge to improve the processes of forming foods, and to design foods that take advantage of the physical properties of lipids to form desired structures. The composition and the structure of lipids affects the rate and pathways of their oxidation that will be measured by direct analysis of oxidation products by Mass Spectrometry. Research will define food structures and compositions that minimize oxidation according to the formation of oxidation products. The physical properties of various length scale lipid particles will be analyzed by optical, NMR and light scattering methodologies. Living organisms, yeast, C. elegans, bacteria will be analyzed for a variety of metabolites including fatty acids, phospholipids and membrane components. Quantitative metabolic profiles will be analyzed by various computational methods to determine the biochemical pathways affected by lipid composition. Bioinformatic and experimental approaches will be used to explore various genomes for the genes responsible for lipid synthesis. Genomic databases will be examined for genes consistent with expression during lactation by 1) literature precedent, 2) known function, 3) promoter activation by known lactation hormone elements, and 4) promoter activation by consensus sequences to known lactation genes. Pathways of lactation activity will be prepared and annotated according to putative nutritional functions. Functions will be confirmed in collaboration with microbiologists, physiologists and nutritionists at UC Davis and around the country.

Progress 10/01/12 to 09/30/17

Outputs
Target Audience:The target audience of the research is to the scientists, policy makers and technologists who support and innovate in the agriculture, food and health industries. We have used different means and media to reach this audience including published articles, presentations, conferences and media. The highlights of the approaches to reach the scientific audience during the progress period were the 2-International conferences that were co-organized and managed: the International Milk Genomics Consortium Project dedicated to assembling the genes responsible for lactation in a broad range of mammals held its 14th annual meeting of the consortium at Quebec City in Canada in October 2017 with 80 scientists and industry representatives from around the world. The conference on human milk composition and innovation was co-organized with Nestle research foundation and attracted 100 attendees in Lausanne, Switzerland in November 2017. Additional presentations during this period are listed below. Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided?Three post-doctoral fellows have been trained during the period in various aspects of project design, management and execution. Bethany Henrick, Sarah Schaeffer and Ishita Shaw, are continuing. During this period 2 graduate students have moved to completion of the advanced degrees, Megan Sanctuary, and Luis Garay Almeda. Junai Gan, continues to proceed successfully towards her degree. Ten undergraduate students were trained in research and analysis techniques appropriate to the mission of the program including milk analysis, clinical study management and publication preparation. How have the results been disseminated to communities of interest?The products from this project have been disseminated through a total of 20 national and international lectures, seminars and presentations, hosting 2 International scientific meetings and 14 peer reviewed publications. The project has graduated 2 PhD scientists and mentored 10 undergraduate students. What do you plan to do during the next reporting period to accomplish the goals?The research goals of this project are attractive to a range of collaborating scientists that have been recruited to share in the immediate objectives of the research and are actively discovering mechanisms of food actions. We are working to extend the research to applications for that knowledge both within the scientific community and to stake holders across the agriculture, food and health industries. We will publish all results in the peer reviewed literature and to present their implications to the larger issues of human health and agricultural sustainability, to report to the scientific community in person and where appropriate to patent components and technologies to provide commercialization opportunities as appropriate. We will support this project and its goals by pursuing competitive funding from International, Federal and State agencies and from Industrial sponsors by engaging directly with strategic industrial partners to translate our discoveries into agricultural and product value and to join with appropriate foundations who have shared visions for the application of scientific discoveries into products and services that improve the human condition. We intend to use the funds brought into the program to recruit, train and promote students, post-doctoral fellows and visiting scientists. The goal of the scientific research and its implications are to enhance the knowledge of food composition and function and to apply that knowledge into agricultural commodities, food processing technologies and human monitoring technologies. Where no other translational agencies are possible we will continue to work with the University Technology Transfer Agency to establish intellectual property and to begin new corporate entities as the commercial means to carry the scientific research findings into the marketplace to improve foods and human health.

Impacts
What was accomplished under these goals? The project continues to build teams of diverse scientists across several disciplines with the shared goal of building the critical knowledge of the relationship between diet and health and to assemble the scientific evidence that both essential and non-essential nutrients, including components from milk and plant secondary compounds, are present, absorbed, metabolized and biologically-active towards metabolic and chemical processes in animals and humans. The scientific studies that we have and are continuing to conduct extend from computational models to actual human clinical trials with the explicit intent to discover how biological processes in humans -- from metabolism to physiology --respond to food components and how to alter both dietary components and entire diets can guide these processes to improve overall health The discoveries on digestion, the structures of food and their metabolism in humans during the reporting period have continued to highlight the importance of digestion of biopolymers to individuals under different health conditions. The importance of digestion to the success of premature and full term babies has been overlooked and our discoveries that enzymes within human milk are critical to the extent and specificity of protein digestion are relevant to many other ages especially to the elderly. These studies also highlight the role of food commodities, their composition, structures and their processing in altering native polymer structure and how these variables contribute to the value of foods. We are constructing a more comprehensive library of these structures and reactivities to catalog the importance of native and explicitly added enzymes to food digestion and health. During this period I was named the Sherman Award recipient by the American Chemical Society for 2018. The thematic center of the research program is guided by the biological processes of mammalian lactation. The distinct biological properties of milk and their role in providing a complete and comprehensive diet to infants provide a model to study human responses to foods across metabolic, immunologic and physiologic processes. The experimental focus is to disassemble milk and understand the structural mechanisms underlying its value to the infant. Our objective is to apply this mechanistic knowledge to the pressing need to intervene proactively in the diets of all humans, i.e. to both prevent disease and demonstrate diagnostically such benefits in actual consumers. We recruit colleagues and funding agencies to the concept that lactation is a biological model for all of agriculture for nutrition, safety and sustainability. The diverse structures and components of milk directly nourish infants, yet they also guide the growth of beneficial intestinal bacteria, protect the intestine from pathogens, shield the intestine from toxins and educate the host's immune system. The lessons learned from milk have led to innovations in food research and product development.

Publications

  • Type: Journal Articles Status: Published Year Published: 2016 Citation: Garrido D, Ruiz-Moyano S, Kirmiz N, Davis JC, Totten SM, Lemay DG, Ugalde JA, German JB, Lebrilla CB, Mills DA. A novel gene cluster allows preferential utilization of fucosylated milk oligosaccharides in Bifidobacterium longum subsp. longum SC596. Sci Rep. 2016 Oct 19;6:35045. doi: 10.1038/srep35045.
  • Type: Journal Articles Status: Published Year Published: 2017 Citation: Garay LA, Sitepu IR, Cajka T, Fiehn O, Cathcart E, Fry RW, Kanti A, Joko Nugroho A, Faulina SA, Stephanandra S, German JB, Boundy-Mills KL. Discovery of synthesis and secretion of polyol esters of fatty acids by four basidiomycetous yeast species in the order Sporidiobolales. J Ind Microbiol Biotechnol. 2017 Jun;44(6):923-936. doi: 10.1007/s10295-017-1919-y. Epub 2017 Mar 13.
  • Type: Journal Articles Status: Published Year Published: 2017 Citation: Tian T, Freeman S, Corey M, German JB, Barile D. Chemical Characterization of Potentially Prebiotic Oligosaccharides in Brewed Coffee and Spent Coffee Grounds. J Agric Food Chem. 2017 Apr 5;65(13):2784-2792. doi: 10.1021/acs.jafc.6b04716. Epub 2017 Mar 28.
  • Type: Book Chapters Status: Published Year Published: 2017 Citation: Dallas DC, German JB. Enzymes in Human Milk. Nestle Nutr Inst Workshop Ser. 2017;88:129-136. doi: 10.1159/000455250. Epub 2017 Mar 27.
  • Type: Journal Articles Status: Published Year Published: 2017 Citation: Karav S, German JB, Rouqui� C, Le Parc A, Barile D. Studying Lactoferrin N-Glycosylation. Int J Mol Sci. 2017 Apr 20;18(4). pii: E870. doi: 10.3390/ijms18040870. Review.
  • Type: Journal Articles Status: Published Year Published: 2017 Citation: Rogers TS, Demmer E, Rivera N, Gertz ER, German JB, Smilowitz JT, Zivkovic AM, Van Loan MD. The role of a dairy fraction rich in milk fat globule membrane in the suppression of postprandial inflammatory markers and bone turnover in obese and overweight adults: an exploratory study. Nutr Metab (Lond). 2017 May 17;14:36. doi: 10.1186/s12986
  • Type: Journal Articles Status: Published Year Published: 2017 Citation: Rogers TS, Demmer E, Rivera N, Gertz ER, German JB, Smilowitz JT, Zivkovic AM, Van Loan MD.The role of a dairy fraction rich in milk fat globule membrane in the suppression of postprandial inflammatory markers and bone turnover in obese and overweight adults: an exploratory study. Nutr Metab (Lond). 2017 May 17;14:36. doi: 10.1186/s12986-017-0189-z. eCollection 2017. PMID: 28529534
  • Type: Journal Articles Status: Published Year Published: 2017 Citation: Garay LA, Sitepu IR, Cajka T, Cathcart E, Fiehn O, German JB, Block DE, Boundy-Mills KL. Simultaneous production of intracellular triacylglycerols and extracellular polyol esters of fatty acids by Rhodotorula babjevae and Rhodotorula aff. paludigena. J Ind Microbiol Biotechnol. 2017 Jul 5. doi: 10.1007/s10295-017-1964-6.
  • Type: Journal Articles Status: Published Year Published: 2017 Citation: O'Sullivan A, Henrick B, Dixon B, Barile D, Zivkovic A, Smilowitz J, Lemay D, Martin W, German JB, Schaefer SE 21st Century Toolkit for Optimizing Population Health through Precision Nutrition. Crit Rev Food Sci Nutr. 2017 Jul 5:0. doi: 10.1080/10408398.2017.1348335.
  • Type: Journal Articles Status: Published Year Published: 2017 Citation: Smilowitz JT, Lemay DG, Kalanetra KM, Chin EL, Zivkovic AM, Breck MA, German JB, Mills DA, Slupsky C, Barile D. Tolerability and safety of the intake of bovine milk oligosaccharides extracted from cheese whey in healthy human adults. J Nutr Sci. 2017 Feb 20;6:e6. doi: 10.1017/jns.2017.2.
  • Type: Journal Articles Status: Published Year Published: 2017 Citation: Karav S, German JB, Rouqui� C, Le Parc A, Barile D Studying Lactoferrin N-Glycosylation. Int J Mol Sci. 2017 Apr 20;18(4). pii: E870. doi: 10.3390/ijms18040870. Review. PMID: 28425960
  • Type: Journal Articles Status: Published Year Published: 2017 Citation: Shih PB, Morisseau C, Le T, Woodside B, German JB Personalized polyunsaturated fatty acids as a potential adjunctive treatment for anorexia nervosa. Prostaglandins Other Lipid Mediat. 2017 Nov;133:11-19. doi: 10.1016/j.prostaglandins.2017.08.010. Epub 2017 Sep 2. PMID: 28873340
  • Type: Journal Articles Status: Published Year Published: 2017 Citation: Gan J, Bornhorst GM, Henrick BM, German JB. Protein Digestion of Baby Foods: Study Approaches and Implications for Infant Health. Mol Nutr Food Res. 2017 Sep 11. doi: 10.1002/mnfr.201700231


Progress 10/01/15 to 09/30/16

Outputs
Target Audience:The target audience of the research includes scientists, policy makers and the food and health industries. We have used various mechanisms to reach this audience including published articles, presentations, conferences and media. The highlights of the scientific audience during the progress period were the 4 -International conferences that were organized and managed: the International Milk Genomics Consortium Project dedicated to assembling the genes responsible for lactation in a broad range of mammals hosted the 13th annual meeting of the consortium at Davis California October 2016 with 100 scientists and industry representatives from around the world. The Fourth International conference on human milk science and innovation was co-organized with Prolacta Biosciences and attracted 70 attendees in Los Angeles October 2016. A workshop was organized jointly between UC Davis and AgResearch New Zealand in October 2016. A conference was jointly organized on Nutrigenomics in Tel Aviv Israel in 2016. Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided?Three post-doctoral fellows have been trained during the period in various aspects of project design, management and execution. Bethany Henrick, Sarah Schaeffer and Ishita Shaw, are continuing. During this period 3 graduate students have been moving towards completion of the advanced degrees, Megan Sanctuary, Junai Wan and Luis Garay Almeda. Twelve undergraduate students were trained in research and analysis techniques appropriate to the mission of the program including milk analysis, clinical study management and publication preparation. How have the results been disseminated to communities of interest?We have used various mechanisms to reach this audience including published articles, presentations, conferences and media. The highlights of the scientific audience during the progress period were the 4 -International conferences that were organized and managed: the International Milk Genomics Consortium Project dedicated to assembling the genes responsible for lactation in a broad range of mammals hosted the 13th annual meeting of the consortium at Davis California October 2016 with 100 scientists and industry representatives from around the world. The Fourth International conference on human milk science and innovation was co-organized with Prolacta Biosciences and attracted 70 attendees in Los Angeles October 2016. A workshop was organized jointly between UC Davis and AgResearch New Zealand in October 2016. A conference was jointly organized on Nutrigenomics in Tel Aviv Israel in 2016. Additional presentations during this period are listed below. German JB 'The Future of Food: Personal, Global Digital' Food Business School Culinary Institute of America, St Helena CA invited lecture German JB The Future of Food High Value Nutrition Conference Auckland University Auckland New Zealand 2016 invited lecture German JB Milk: a model to understand diet-microbiota interactions. Conference on Prebiotics and Probiotics Evoniks Frankfurt Germany invited lecture 2016 German JB 10th Annual Congress of the International Society of Nurigenomics and Nutrigenetics Tel Aviv Israel co-organizer & chair Nutrigenomics of Milk and Lactation May 22-26 2016 German JB Lactation - Evolving Components of Health 10th Annual Congress of the International Society of Nurigenomics and Nutrigenetics Tel Aviv Israel Invited Lecture May 24 2016 German JB Human Milk Oligosaccharides for Environmental Enteric Dysfunction Workshop. Bill and Melinda Gates Foundation co-organizer and invited lecture Seattle WA May 16 2016 German J.B. Gilbert Leveille Award and Lecture Institute for Food Technology 2015 'What can Lactation and Milk teach us about the Future of Diet and Health' Chicago 2016 German JB International Milk Genomics Consortium Annual Meeting -Organizer and chair, Introduction: 14 years of Milk Genomics, A Retrospective. Davis CA 2016 German JB German JB Co-Organizer, Introduction and discussion in: Fourth International Congress on Human Milk Science and Innovation. Los Angeles California 2016 German JB Oligosaccharides and the infant Microbiome Symposium Series on Infant Health Cancun Mexico 2016 German JB 'Milk and Lactation, a roadmap for scientific innovation and industrial translation for Food and Health Invited Lecture University of Nebraska, Lincoln, 2016 German JB 'Milk and Health' UC Davis/Chile Invited Lecture Santiago Chile 2016 German JB 'History of Davis - Dublin collaborations' John E Kinsella Memorial Symposium Introductory Lecture Davis CA 2016 German JB ' Milk and the Microbiome of Infants ' Invited Lecture Haas School of Business University of California, Berkeley 2016 What do you plan to do during the next reporting period to accomplish the goals?The scientists recruited to share in the objectives of this project are actively discovering new mechanisms of food actions. We are working to provide applications for that knowledge both within the scientific community and to stake holders across the agriculture, food and health industries. We will continu to publish all results in the peer reviewed literature and to interpret their implications to the larger issues of human health and agricultural sustainability, to report to the scientific community in person and where appropriate to patent components and technologies to provide commercialization opportunities as appropriate. We will continue to support this overall project and its goals by pursuing competitive funding from Federal and State agencies, by engaging with strategic industrial partners to develop the scientific discoveries into agricultural and product value and to join with appropriate foundations who have shared visions for the application of scientific discoveries into products and services that improve the human condition. We will apply the funds brought into the program to recruit, train and promote students, post-doctoral fellows and visiting scientists. The logical path for the scientific discoveries and their implications are to enhance the knowledge of food and to apply that knowledge into agricultural commodities, food processing technologies and human monitoring technologies. Where no other translational agencies are possible we will consider launching new corporate entities as the commercial means to carry the scientific research findings into the marketplace to improve foods and human health.

Impacts
What was accomplished under these goals? The project now well over a decade into its progress continues to build teams of diverse scientists across several disciplines with the shared goal of building actionable knowledge of the relationship between diet and health and assemble the scientific evidence that both essential and non-essential nutrients, including components from milk and plant secondary compounds, are present, absorbed, metabolized and biologically-active towards metabolic and chemical processes in animals and humans. Studies span the range from computational models to actual human clinical trials are all designed to discover how biological processes in humans -- from metabolism to physiology --respond to food components and how to alter both dietary components and entire diets can guide these processes to improve overall health The discoveries on metabolism in humans during the reporting period have continued to highlight the importance of digestion of biopolymers to individuals under different health conditions. The importance of digestion to the success of premature and full term babies has been overlooked and our discoveries that enzymes within human milk are critical to the extent and specificity of protein digestion are relevant to many other ages especially to the elderly. These studies also highlight the role of food commodity origins and their processing in altering native polymer structure and how this in turn alters the value of foods. We are constructing a more comprehensive library of these structures and reactivities to catalog the importance of native and explicitly added enzymes to food digestion and health. The thematic center of the research program is increasingly focused on the biological processes of mammalian lactation. The diverse biological properties of milk provide for our research a biological and chemical model to study and understand human responses to foods across metabolic, immunologic and physiologic processes. The specific focus of this research is to disassemble milk in order to understand the mechanisms by which it provides value to the infant while minimizing the cost to the mother. Our ultimate objective is to take this mechanistic knowledge as the rationale to intervene proactively, i.e. to both prevent disease and demonstrate diagnostically how. We have continued to recruit colleagues and funding agencies to the concept that lactation is a biological model for all of agriculture for nutrition, safety and sustainability. The diverse structures and components of milk nourish infants guide the growth of beneficial intestinal bacteria, protect the intestine from pathogens, protect the intestine from toxins and educate the host's immune system. The lessons learned from milk have led to innovations in food research and product development.

Publications

  • Type: Journal Articles Status: Published Year Published: 2016 Citation: Lewis ZT, Davis JC, Smilowitz JT, German JB, Lebrilla CB, Mills DA. The impact of freeze-drying infant fecal samples on measures of their bacterial community profiles and milk-derived oligosaccharide content. PeerJ. 2016 Jan 21;4:e1612. doi: 10.7717/peerj.1612. eCollection 2016. PMID: 26819854
  • Type: Journal Articles Status: Published Year Published: 2016 Citation: Garay LA, Sitepu IR, Cajka T, Chandra I, Shi S, Lin T, German JB, Fiehn O, Boundy-Mills KL. Eighteen new oleaginous yeast species. J Ind Microbiol Biotechnol. 2016 Apr 12. [Epub ahead of print PMID: 27072563
  • Type: Journal Articles Status: Published Year Published: 2016 Citation: Henrick BM, Yao XD, Taha AY, German JB, Rosenthal KL. Insights into Soluble Toll-Like Receptor 2 as a Downregulator of Virally Induced Inflammation. Front Immunol. 2016 Aug 2;7:291. doi: 10.3389/fimmu.2016.00291. Review.
  • Type: Journal Articles Status: Published Year Published: 2015 Citation: Berthelot CC, Kamita SG, Sacchi R, Yang J, Nording ML, Georgi K, Hegedus Karbowski C, German JB, Weiss RH, Hogg RJ, Hammock BD, Zivkovic AM. Changes in PTGS1 and ALOX12 Gene Expression in Peripheral Blood Mononuclear Cells Are Associated with Changes in Arachidonic Acid, Oxylipins, and Oxylipin/Fatty Acid Ratios in Response to Omega-3 Fatty Acid Supplementation. PLoS One. 2015 Dec 16;10(12):e0144996. doi: 10.1371/journal.pone.0144996. eCollection 2015. PMID: 26672987
  • Type: Journal Articles Status: Published Year Published: 2015 Citation: Pudlo NA, Urs K, Kumar SS, German JB, Mills DA, Martens EC. Symbiotic Human Gut Bacteria with Variable Metabolic Priorities for Host Mucosal Glycans. MBio. 2015 Nov 10;6(6):e01282-15. doi: 10.1128/mBio.01282-15. PMID: 26556271
  • Type: Journal Articles Status: Published Year Published: 2016 Citation: Awasthi S, Wilken R, Patel F, German JB, Mills DA, Lebrilla CB, Kim K, Freeman SL, Smilowitz JT, Armstrong AW, Maverakis E. Dietary supplementation with Bifidobacterium longum subsp. infantis (B. infantis) in healthy breastfed infants: study protocol for a randomised controlled trial. Trials. 2016 Jul 22;17(1):340. doi: 10.1186/s13063-016-1467-1. PMID: 27449926
  • Type: Journal Articles Status: Published Year Published: 2016 Citation: Davis JC, Totten SM, Huang JO, Nagshbandi S, Kirmiz N, Garrido DA, Lewis ZT, Wu LD, Smilowitz JT,German JB, Mills DA, Lebrilla CB. Identification of Oligosaccharides in Feces of Breast-fed Infants and Their Correlation with the Gut Microbial Community. Mol Cell Proteomics. 2016 Sep;15(9):2987-3002. doi: 10.1074/mcp.M116.060665. PMID: 27435585
  • Type: Journal Articles Status: Published Year Published: 2016 Citation: Demmer E, Van Loan MD, Rivera N, Rogers TS, Gertz ER, German JB, Zivkovic AM, Smilowitz JT. Consumption of a high-fat meal containing cheese compared with a vegan alternative lowers postprandial C-reactive protein in overweight and obese individuals with metabolic abnormalities: a randomised controlled cross-over study. J Nutr Sci. 2016 Feb 9;5:e9. doi: 10.1017/jns.2015.40. PMID: 27313852
  • Type: Journal Articles Status: Published Year Published: 2016 Citation: Demmer E, Van Loan MD, Rivera N, Rogers TS, Gertz ER, German JB, Smilowitz JT, Zivkovic AM. Addition of a dairy fraction rich in milk fat globule membrane to a high-saturated fat meal reduces the postprandial insulinaemic and inflammatory response in overweight and obese adults. J Nutr Sci. 2016 Mar 7;5:e14. doi: 10.1017/jns.2015.42 PMID: 27313850
  • Type: Journal Articles Status: Published Year Published: 2016 Citation: Huang J, Kailemia MJ, Goonatilleke E, Parker EA, Hong Q, Sabia R, Smilowitz JT, German JB, Lebrilla CB Quantitation of human milk proteins and their glycoforms using multiple reaction monitoring (MRM). Anal Bioanal Chem. 2016 Oct 29. PMID: 27796459
  • Type: Journal Articles Status: Published Year Published: 2016 Citation: Xu G, Davis JC, Goonatilleke E, Smilowitz JT, German JB, Lebrilla CB. Absolute Quantitation of Human Milk Oligosaccharides Reveals Phenotypic Variations during Lactation. J Nutr. 2016 Oct 19. pii: jn238279
  • Type: Journal Articles Status: Published Year Published: 2016 Citation: Garrido D, Ruiz-Moyano S, Kirmiz N, Davis JC, Totten SM, Lemay DG, Ugalde JA, German JB, Lebrilla CB, Mills DA. A novel gene cluster allows preferential utilization of fucosylated milk oligosaccharides in Bifidobacterium longum subsp. longum SC596. Sci Rep. 2016 Oct 19;6:35045. doi: 10.1038/srep35045
  • Type: Journal Articles Status: Published Year Published: 2015 Citation: Dallas DC, Sanctuary MR, Qu Y, Khajavi SH, Van Zandt AE, Dyandra M, Frese SA, Barile D, German JB. Personalizing Protein Nourishment. Crit Rev Food Sci Nutr. 2015 Dec 29:0. [Epub ahead of print] PMID: 26713355


Progress 10/01/14 to 09/30/15

Outputs
Target Audience:The target audience of the research includes scientists, policy makers and the food and health industries. We have used various mechanisms to reach this audience including published articles, presentations, conferences and media. We co-organized 2 conferences: the International Milk Genomics Consortium Project dedicated to assembling the genes responsible for lactation in a broad range of mammals hosted the 12th annual meeting of the consortium at Sydney Australia October 2015 with 100 scientists and industry representatives from around the world. The third International conference on human milk science and innovation was co-organized with Prolacta Biosciences and attracted 70 attendees in Los Angeles October 2015. Additional presentations during this period are listed below. German JB 'Food Innovation, an Institutional Approach at the University of California' Seed Central Conference University of California, Davis 2015 http://www.seedcentral.org/presentations/pdf/German_Bruce_January2015.pdf German JB 'The Future of Scientific Research in Food Science Technology Engineering Math STEM at its finest Davis High Science Curriculum 2015 German JB Innovation in Agriculture and Food: The Future of Disruptive Innovation to Scale San Francisco Hackathon 2015 http://foodhackathon.co German JB Where is the world of science heading? AgResearch New Zealand Science Conference 2015 Palmerston North New Zealand 2015 invited lecture German JB When Food meets Silicon - The Knowledge based Future of Diet and Health fast Innovator Conference, Laval University, Quebec, Canada invited lecture 2015 German JB Innovation Communication - How do you explain 'good germs'? World Food Center Conference on Food Literacy Davis CA 2015 German JB Lactation as a model for Guiding Biology' in FASEB Conference "Origins and Benefits of Biologically-Active Components of Human Milk" Big Sky Montana 2015 German JB Dietary fat in the diet - a view from the perspective of babies. San Francisco Professional Food Society invited lecture and workshop 2015 German JB Evolutionary Diet and Health: what can lactation teach us about biology, diet and health. Arizona State University invited Lecture Phoenix Arizona 2015 German JB Introduction and discussion in: Third International Congress on Human Milk Science and Innovation. Los Angeles California 2015 German JB Global Health Platform Conference Nashville TN Workshop: Agriculture and Food, Milk and lactation as Scientific models 2015 German JB The Future of diet and health, Personal, Active and Protective. Hong Kong Nutrition Society Conference, Hong Kong 2015 German JB Lactation as a model for Research and Innovation. Harvard University and Massachusetts General Hospital invited lecture 2015 German JB Life in the small world - the microbiota of breast fed babies San Francisco Exploratorium invited Public lecture 2015 Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided?Two post-doctoral fellows have been trained during the period in various aspects of project design, management and execution. Bethany Henricks and David Dallas, are continuing. During this period 4 graduate students have been moving towards completion of the advanced degrees, Bonnie Dixon, Megan Sanctuary, Junai Wan and Jacky Moya. Fifteen undergraduate students were trained in research and analysis techniques appropriate to the mission of the program including milk analysis, clinical study management and publication preparation. How have the results been disseminated to communities of interest?German JB 'Food Innovation, an Institutional Approach at the University of California' Seed Central Conference University of California, Davis 2015 http://www.seedcentral.org/presentations/pdf/German_Bruce_January2015.pdf German JB 'The Future of Scientific Research in Food Science Technology Engineering Math STEM at its finest Davis High Science Curriculum 2015 German JB Innovation in Agriculture and Food: The Future of Disruptive Innovation to Scale San Francisco Hackathon 2015 http://foodhackathon.co German JB Where is the world of science heading? AgResearch New Zealand Science Conference 2015 Palmerston North New Zealand 2015 invited lecture German JB When Food meets Silicon - The Knowledge based Future of Diet and Health fast Innovator Conference, Laval University, Quebec, Canada invited lecture 2015 German JB Innovation Communication - How do you explain 'good germs'? World Food Center Conference on Food Literacy Davis CA 2015 German JB Lactation as a model for Guiding Biology' in FASEB Conference "Origins and Benefits of Biologically-Active Components of Human Milk" Big Sky Montana 2015 German JB Dietary fat in the diet - a view from the perspective of babies. San Francisco Professional Food Society invited lecture and workshop 2015 German JB Evolutionary Diet and Health: what can lactation teach us about biology, diet and health. Arizona State University invited Lecture Phoenix Arizona 2015 German JB Introduction and discussion in: Third International Congress on Human Milk Science and Innovation. Los Angeles California 2015 German JB Global Health Platform Conference Nashville TN Workshop: Agriculture and Food, Milk and lactation as Scientific models 2015 German JB The Future of diet and health, Personal, Active and Protective. Hong Kong Nutrition Society Conference, Hong Kong 2015 German JB Lactation as a model for Research and Innovation. Harvard University and Massachusetts General Hospital invited lecture 2015 German JB Life in the small world - the microbiota of breast fed babies San Francisco Exploratorium invited Public lecture 2015 What do you plan to do during the next reporting period to accomplish the goals?All scientists involved in this project have been assembled to discover new mechanisms of food actions, develop these discoveries into quantitative and qualitatively accurate scientific evidence, to publish all results in the peer reviewed literature and to interpret their implications to the larger issues of human health and agricultural sustainability, to report to the scientific community in person and where appropriate to patent components and technologies to provide commercialization opportunities as appropriate. We will continue to support this overall project and its goals by pursuing competitive funding from Federal and State agencies, by engaging with strategic industrial partners to develop the scientific discoveries into agricultural and product value and to join with appropriate foundations who have shared visions for the application of scientific discoveries into products and services that improve the human condition. We will apply the funds brought into the program to recruit, train and promote students, post-doctoral fellows and visiting scientists. The logical path for the scientific discoveries and their implications are to enhance the knowledge of food and to apply that knowledge into agricultural commodities, food processing technologies and human monitoring technologies. Where no other translational agencies are possible we will consider launching new corporate entities as the commercial means to carry the scientific research findings into the marketplace to improve foods and human health.

Impacts
What was accomplished under these goals? The project continues to assemble diverse scientists and disciplines into the objectives of to building the scientific evidence that both essential and non-essential nutrients, including components from milk and plant secondary compounds, are present, absorbed, metabolized and biologically-active towards metabolic and chemical processes in animals and humans. Experiments are all designed to discover how biological processes in humans -- from metabolism to physiology --respond to food components and how to alter both dietary components and entire diets can guide these processes to improve overall health The discoveries on metabolism during the past year illustrate the importance of digestion of biopolymers to multiple targets. The importance of digestion to the health of everyone from babies to the elderly highlight the role of native polymer structure and its reactions to process engineering in the value of foods. We have begun to catalog the importance of native and explicitly added enzymes to food digestion and health traits. The thematic center of the research program is the remarkable biological processes of lactation. The nourishing properties of milk are used as a biological and chemical model to understand human responses to foods across metabolic, immunologic and physiologic processes. The specific focus of this research is to understand these processes well enough to intervene proactively, i.e. for prevention of disease rather than its diagnosis and therapeutic management. Lactation is a biological model for all of agriculture as scientists seek to develop innovations in nutrition, safety and sustainability necessary to successfully feed 9 billion people in the 21st century. The chemical components of milk that nourish infants have been found to also guide the growth of beneficial intestinal bacteria, protect the intestine from pathogens, protect the intestine from toxins and educate the host's immune system. The lessons learned from milk have led to innovations in food research and product development.

Publications

  • Type: Journal Articles Status: Published Year Published: 2014 Citation: De Leoz ML, Kalanetra KM, Bokulich NA, Strum JS, Underwood MA, German JB, Mills DA, Lebrilla CB. Human Milk Glycomics and Gut Microbial Genomics in Infant Feces Shows Correlation between Human Milk Oligosaccharides and Gut Microbiota: A Proof-of-Concept Study. J Proteome Res. 2014 Oct 10
  • Type: Journal Articles Status: Published Year Published: 2014 Citation: Underwood MA, German JB, Lebrilla CB, Mills DA. Bifidobacterium longum subspecies infantis: champion colonizer of the infant gut. Pediatr Res. 2014 Oct 10. doi: 10.1038/pr.2014.156
  • Type: Journal Articles Status: Published Year Published: 2014 Citation: Grapov D, Lemay DG, Weber D, Phinney BS, Chertok I, Gho DS, German JB, Smilowitz JT. The Human Colostrum Whey Proteome is Altered in Gestational Diabetes Mellitus. J Proteome Res. 2014 Oct 22
  • Type: Journal Articles Status: Published Year Published: 2015 Citation: 5. German J Bruce, Jennifer T Smilowitz, Carlito B Lebrilla, David A Mills, Samara L Freeman, Metabolomics and Milk: The Development of the Microbiota in Breastfed Infants in Metabonomics and Gut Microbiota in Nutrition and Disease Springer London 1/1 2015 147-167
  • Type: Journal Articles Status: Published Year Published: 2014 Citation: Totten SM, Wu LD, Parker EA, Davis JC, Hua S, Stroble C, Ruhaak LR, Smilowitz JT, German JB, Lebrilla CB. Rapid-throughput glycomics applied to human milk oligosaccharide profiling for large human studies.Anal Bioanal Chem. 2014 Oct 31.
  • Type: Journal Articles Status: Published Year Published: 2014 Citation: Holton TA, Vijayakumar V, Dallas DC, Guerrero A, Borghese RA, Lebrilla CB, German JB, Barile D, Underwood MA, Shields DC, Khaldi N. Following the Digestion of Milk Proteins from Mother to Baby.J Proteome Res. 2014 Nov 11
  • Type: Journal Articles Status: Published Year Published: 2014 Citation: Dallas DC, Guerrero A, Parker EA, Robinson RC, Gan J, German JB, Barile D, Lebrilla CB. Current peptidomics: Applications, purification, identification, quantification, and functional analysis.Proteomics. 2014 Nov 27. doi: 10.1002/pmic.201400310
  • Type: Journal Articles Status: Published Year Published: 2015 Citation: A Dashipour, V Razavilar, H Hosseini, S Shojaee-Aliabadi, JB German, Kiandokht Ghanati, Mansour Khakpour, Ramin Khaksar. Antioxidant and antimicrobial carboxymethyl cellulose films containing Zataria multiflora essential oil International journal of biological macromolecules 72, 606-613
  • Type: Journal Articles Status: Published Year Published: 2015 Citation: Dallas DC, Smink CJ, Robinson RC, Tian T, Guerrero A, Parker EA, Smilowitz JT, Hettinga KA, Underwood MA, Lebrilla CB, German JB, Barile D. Endogenous human milk Peptide release is greater after preterm birth than term birth. J Nutr. 2015 Mar;145(3):425-33. doi: 10.3945/jn.114.203646
  • Type: Journal Articles Status: Published Year Published: 2015 Citation: Huang J, Guerrero A, Parker E, Strum JS, Smilowitz JT, German JB, Lebrilla CB Site-specific glycosylation of secretory immunoglobulin a from human colostrum. J Proteome Res. 2015 Mar 6;14(3):1335-49. doi: 10.1021/pr500826q
  • Type: Conference Papers and Presentations Status: Published Year Published: 2015 Citation: German J.B. Milk Lipids: Molecules to Structures to Functions. Proceedings of the Second Annual International Conference on Human Milk Science and Innovation. Prolacta Bioscience Inc.
  • Type: Journal Articles Status: Published Year Published: 2015 Citation: Shih PB, Yang J, Morisseau C, German JB, Zeeland AA, Armando AM, Quehenberger O, Bergen AW, Magistretti P, Berrettini W, Halmi KA, Schork N, Hammock BD, Kaye W. Dysregulation of soluble epoxide hydrolase and lipidomic profiles in anorexia nervosa. Mol Psychiatry. 2015 Mar 31. doi: 10.1038/mp.2015.26
  • Type: Journal Articles Status: Published Year Published: 2015 Citation: Lewis ZT, Totten SM, Smilowitz JT, Popovic M, Parker E, Lemay DG, Van Tassell ML, Miller MJ, Jin YS, German JB, Lebrilla CB, Mills DA. Maternal fucosyltransferase 2 status affects the gut bifidobacterial communities of breastfed infants. Microbiome. 2015 Apr 10;3:13. doi: 10.1186/s40168-015-0071-z
  • Type: Journal Articles Status: Published Year Published: 2015 Citation: Guerrero A, Dallas DC, Contreras S, Bhandari A, C�novas A, Islas-Trejo A, Medrano JF, Parker EA, Wang M, Hettinga K, Chee S, German JB, Barile D, Lebrilla CB Peptidomic analysis of healthy and subclinically mastitic bovine milk. Int Dairy J. 2015 Jul 1;46:46-52
  • Type: Journal Articles Status: Published Year Published: 2015 Citation: Spevacek AR, Smilowitz JT, Chin EL, Underwood MA, German JB, Slupsky CM. Infant Maturity at Birth Reveals Minor Differences in the Maternal Milk Metabolome in the First Month of Lactation. J Nutr. 2015 Jun 3. pii: jn210252
  • Type: Journal Articles Status: Published Year Published: 2015 Citation: Schaefer SE, Camacho-Gomez R, Sadeghi B, Kaiser L, German JB, de la Torre A. Assessing Child Obesity and Physical Activity in a Hard-to-Reach Population in Californias Central Valley, 2012-2013. Prev Chronic Dis. 2015 Jul 23;12:E117. doi: 10.5888/pcd12.140577
  • Type: Journal Articles Status: Published Year Published: 2015 Citation: Underwood MA, Gaerlan S, De Leoz ML, Dimapasoc L, Kalanetra KM, Lemay DG, German JB, Mills DA, Lebrilla CB. Human milk oligosaccharides in premature infants: absorption, excretion, and influence on the intestinal microbiota. Pediatr Res. 2015 Aug 31. doi: 10.1038/pr.2015.162
  • Type: Journal Articles Status: Published Year Published: 2015 Citation: 19. Garrido D, Ruiz-Moyano S, Lemay DG, Sela DA, German JB, Mills DA. Comparative transcriptomics reveals key differences in the response to milk oligosaccharides of infant gut-associated bifidobacteria. Sci Rep. 2015 Sep 4;5:13517. doi: 10.1038/srep13517


Progress 10/01/13 to 09/30/14

Outputs
Target Audience: The target audience of the research includes scientists, policy makers and the food and health industries. We have used various mechanisms to reach this audience including published articles, presentations, conferences and media. We co-organized 2 conferences: the International Milk Genomics Consortium Project dedicated to assembling the genes responsible for lactation in a broad range of mammals hosted the 11th annual meeting of the consortium at Aarhus Denmark October 2014 with 125 scientists and industry representatives from around the world. The second International conference on human milk science and innovation was co-organized with Prolacta Biosciences and attracted 70 attendees in Los Angeles November 2014. The target audience of the research includes scientists, policy makers and the food and health industries. We have used various mechanisms to reach this audience including published articles, presentations, conferences and media. We co-organized 2 conferences: the International Milk Genomics Consortium Project dedicated to assembling the genes responsible for lactation in a broad range of mammals hosted the 11th annual meeting of the consortium at Aarhus Denmark October 2014 with 125 scientists and industry representatives from around the world. The second International conference on human milk science and innovation was co-organized with Prolacta Biosciences and attracted 70 attendees in Los Angeles November 2014. Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided? Two post-doctoral fellows have been trained during the period in various aspects of project design, management and execution. Felicia Goldsmith, David Dallas, are continuing. During this period 4 graduate students have been moving towards completion of the advanced degrees, Bonnie Dixon, Megan Sanctuary, Junai Wan and Bill Martin. Twenty undergraduate students were trained in research and analysis techniques appropriate to the mission of the program including milk analysis, clinical study management and publication preparation. How have the results been disseminated to communities of interest? German JB Oregon Statue University Food Nutrition and Health Update 2014 "Personalized Nutrition and Nutrigenomics - What it Means for Food" Corvallis Oregon Feb 25 2014 German JB Organizer: Conference on Coffee Research in the 21st century: Introduction to conference - Foods for Health as a model for innovation and translation. German JB Lactation The importance of feeding babies and bacteria. Science Café University of California, Davis. Davis California May 2014 Danielle Lemay, Russell Hovey, Stella Hartono, Katie Hinde, Jennifer Smilowitz, Frank Ventimiglia, Kimberli Schmidt, Joyce Lee, Alma Islas-Trejo, Juan Medrano, Ian Korf, Peter Barry, J German Sequencing the transcriptome of milk production: milk trumps mammary tissue (622.2) Experimental Biology 2014 San Diego CA David Dallas, Andres Guerrero, Nora Khaldi, Evan Parker, Patricia Castillo, Mark Underwood, Charles Bevins, Carlito Lebrilla, J German, Daniela Barile Experimental Biology San Diego CA 2014 German JB Metabolomics and Milk A model for diet and health SciX Conference Reno Nevada invited lecture 2014 German JB Foods for Health: A focus for International Collaboration UC Davis UC Dublin joint conference at the John E Kinsella Lecture, Irish Embassy Washington DC 2014 German JB Introduction & Summary, International Milk Genomics Consortium 11th Anniversary conference. Aarhus Denmark 2014 German JB Keynote Lecture: Ten years of IMGC: Mining the Evolution of Milk and Lactation Weihenstephan Dairy Conference Freisling Germany 2014 German JB invited lecture Shaping the Gut Microbiome by Milk Oligosaccharides, International Society for Research in Human Milk and Lactation 17th Conference South Carolina USA German JB TechCon Conference AgTech - Investing in the Future of Agriculture - Creating value through Health Sacramento California 2014 German JB co-organizer: Second International Congress on Human Milk Science and Innovation. Los Angeles California 2014 German JB Milk Lipids from composition to Function in: Second International Congress on Human Milk Science and Innovation. Los Angeles California German JB Global Health Platform Conference Nashville TN Workshop: Creating Innovation in Agriculture and Food, Milk and lactation as Scientific models 2014 What do you plan to do during the next reporting period to accomplish the goals? We will continued to develop scientific evidence publish results and their implications, report to the scientific community in person and patent components and technologies to provide commercialization opportunities as appropriate. We will continue to pursue funding from Federal and State agencies, industrial partners and appropriate foundations. We will leverage that funding to recruit, train and promote students, post-doctoral fellows and visiting scientists. Where no other translational agencies are possible we will consider launching new corporate entities as the commercial means to carry the scientific research findings into the marketplace to improve foods and human health.

Impacts
What was accomplished under these goals? The team assembled into the projects continues to build the scientific evidence that non-essential nutrients, including components from milk and plant secondary compounds, are absorbed, metabolized and biologically-active towards metabolic and chemical processes in animals and humans. The studies all conducted in parallel are designed to understand how human metabolism-- targeting for example fatty acid biochemistry--is responsive to diet and how to alter dietary components including lipids to improve specific aspects of overall health The results of our research to understand lipid metabolism imply that alterations in food would be an accessible and appropriate means to achieve targeted alterations in metabolism maximizing efficacy and safety. Many of these alterations will require modifications in production agriculture and process engineering of foods to achieve. With this goal in mind we have also continued to build knowledge on the composition and functions of commodities, in particular, the lipid components of foods. All projects are taking advantage of our increasing understanding of and access to the various biological dimensions of lactation. The biological properties of milk are a roadmap to approaches to foods that will be mechanistically active in enhancing metabolic, immunologic and physiologic processes rather than acting to cure disease. Lactation is a blueprint for all of agriculture and its need to build innovations in nutrition, safety and sustainability. Milk components that selectively stimulate and support the competitive growth of beneficial intestinal bacteria, protect the intestine from pathogens, protect the intestine from toxins and educate the host's immune system. These examples of milk strategies has led us into new approaches to food research and product development.

Publications

  • Type: Conference Papers and Presentations Status: Other Year Published: 2014 Citation: German JB Oregon Statue University Food Nutrition and Health Update 2014 "Personalized Nutrition and Nutrigenomics  What it Means for Food" Corvallis Oregon Feb 25 2014
  • Type: Conference Papers and Presentations Status: Other Year Published: 2014 Citation: German JB Organizer: Conference on Coffee Research in the 21st century: Introduction to conference  Foods for Health as a model for innovation and translation.
  • Type: Conference Papers and Presentations Status: Other Year Published: 2014 Citation: German JB Lactation The importance of feeding babies and bacteria. Science Caf� University of California, Davis. Davis California May 2014
  • Type: Conference Papers and Presentations Status: Other Year Published: 2014 Citation: Danielle Lemay, Russell Hovey, Stella Hartono, Katie Hinde, Jennifer Smilowitz, Frank Ventimiglia, Kimberli Schmidt, Joyce Lee, Alma Islas-Trejo, Juan Medrano, Ian Korf, Peter Barry, J German Sequencing the transcriptome of milk production: milk trumps mammary tissue (622.2) Experimental Biology 2014 San Diego CA
  • Type: Conference Papers and Presentations Status: Other Year Published: 2014 Citation: David Dallas, Andres Guerrero, Nora Khaldi, Evan Parker, Patricia Castillo, Mark Underwood, Charles Bevins, Carlito Lebrilla, J German, Daniela Barile Experimental Biology San Diego CA 2014
  • Type: Conference Papers and Presentations Status: Other Year Published: 2014 Citation: German JB Metabolomics and Milk A model for diet and health SciX Conference Reno Nevada invited lecture 2014 German JB Foods for Health: A focus for International Collaboration UC Davis UC Dublin joint conference at the John E Kinsella Lecture, Irish Embassy Washington DC 2014
  • Type: Conference Papers and Presentations Status: Other Year Published: 2014 Citation: German JB Introduction & Summary, International Milk Genomics Consortium 11th Anniversary conference. Aarhus Denmark 2014
  • Type: Conference Papers and Presentations Status: Other Year Published: 2014 Citation: German JB Keynote Lecture: Ten years of IMGC: Mining the Evolution of Milk and Lactation Weihenstephan Dairy Conference Freisling Germany 2014
  • Type: Conference Papers and Presentations Status: Other Year Published: 2014 Citation: German JB invited lecture Shaping the Gut Microbiome by Milk Oligosaccharides, International Society for Research in Human Milk and Lactation 17th Conference South Carolina USA
  • Type: Conference Papers and Presentations Status: Other Year Published: 2014 Citation: German JB TechCon Conference AgTech  Investing in the Future of Agriculture  Creating value through Health Sacramento California 2014
  • Type: Conference Papers and Presentations Status: Other Year Published: 2014 Citation: German JB co-organizer: Second International Congress on Human Milk Science and Innovation. Los Angeles California 2014
  • Type: Conference Papers and Presentations Status: Other Year Published: 2014 Citation: German JB Milk Lipids from composition to Function in: Second International Congress on Human Milk Science and Innovation. Los Angeles California
  • Type: Conference Papers and Presentations Status: Other Year Published: 2014 Citation: German JB Global Health Platform Conference Nashville TN Workshop: Creating Innovation in Agriculture and Food, Milk and lactation as Scientific models 2014
  • Type: Journal Articles Status: Published Year Published: 2014 Citation: Hong Q, Ruhaak LR, Totten SM, Smilowitz JT, German JB, Lebrilla CB. Label-free absolute quantitation of oligosaccharides using multiple reaction monitoring. Anal Chem. 2014 Mar 4;86(5):2640-7.
  • Type: Journal Articles Status: Published Year Published: 2014 Citation: Smilowitz JT, Gho DS, Mirmiran M, German JB, Underwood MA. Rapid Measurement of Human Milk Macronutrients in the Neonatal Intensive Care Unit: Accuracy and Precision of Fourier Transform Mid-Infrared Spectroscopy. J Hum Lact. 2014 Jan 14.
  • Type: Journal Articles Status: Published Year Published: 2014 Citation: Huang J, Lee H, Zivkovic AM, Smilowitz JT, Rivera N, German JB, Lebrilla CB. Glycomic Analysis of High Density Lipoprotein Shows a Highly Sialylated Particle. J Proteome Res. 2014 Jan 21.
  • Type: Journal Articles Status: Published Year Published: 2014 Citation: Dallas DC, Guerrero A, Parker EA, Garay LA, Bhandari A, Lebrilla CB, Barile D, German JB. Peptidomic Profile of Milk of Holstein Cows at Peak Lactation.J Agric Food Chem. 2013 Dec 23.
  • Type: Journal Articles Status: Published Year Published: 2014 Citation: Lemay DG, Hovey RC, Hartono SR, Hinde K, Smilowitz JT, Ventimiglia F, Schmidt KA, Lee JW, Islas-Trejo A, Silva PI, Korf I, Medrano JF, Barry PA, German JB. Sequencing the transcriptome of milk production: milk trumps mammary tissue. BMC Genomics. 2013 Dec 12;14:872. doi: 10.1186/1471-2164-14-872.
  • Type: Journal Articles Status: Published Year Published: 2014 Citation: Nording ML, Yang J, Georgi K, Hegedus Karbowski C, German JB, Weiss RH, Hogg RJ, Trygg J, Hammock BD, Zivkovic AM Individual variation in lipidomic profiles of healthy subjects in response to omega-3 Fatty acids. PLoS One. 2013 Oct 24;8(10):e76575.
  • Type: Journal Articles Status: Published Year Published: 2014 Citation: Underwood MA, Kalanetra KM, Bokulich NA, Mirmiran M, Barile D, Tancredi DJ, German JB, Lebrilla CB, Mills DA. Prebiotic oligosaccharides in premature infants. J Pediatr Gastroenterol Nutr. 2014 Mar;58(3):352-60. doi:
  • Type: Journal Articles Status: Published Year Published: 2014 Citation: Mehra R, Barile D, Marotta M, Lebrilla CB, Chu C, German JB. Novel high-molecular weight fucosylated milk oligosaccharides identified in dairy streams. PLoS One. 2014 May 8;9(5):e96040.
  • Type: Journal Articles Status: Published Year Published: 2014 Citation: Dallas DC, Guerrero A, Khaldi N, Borghese R, Bhandari A, Underwood MA, Lebrilla CB, German JB, Barile D. A peptidomic analysis of human milk digestion in the infant stomach reveals protein-specific degradation patterns. J Nutr. 2014 Jun;144(6):815-20.
  • Type: Journal Articles Status: Published Year Published: 2014 Citation: Smilowitz JT, Lebrilla CB, Mills DA, German JB, Freeman SL. Breast Milk Oligosaccharides: Structure-Function Relationships in the Neonate. Annu Rev Nutr. 2013 Jul 22.
  • Type: Journal Articles Status: Published Year Published: 2014 Citation: Khaldi N, Vijayakumar V, Dallas DC, Guerrero A, Wickramasinghe S, Smilowitz JT, Medrano JF, Lebrilla CB, Shields DC, German JB. Predicting the important enzyme players in human breast milk digestion. J Agric Food Chem. 2014 Mar 12.
  • Type: Journal Articles Status: Published Year Published: 2014 Citation: Schaefer SE, Van Loan M, German JB.A feasibility study of wearable activity monitors for pre-adolescent school-age children. Prev Chronic Dis. 2014 May 22;11:E85.
  • Type: Journal Articles Status: Published Year Published: 2014 Citation: German JB. The future of yogurt: scientific and regulatory needs. Am J Clin Nutr. 2014 May;99(5 Suppl):1271S-8S.
  • Type: Journal Articles Status: Published Year Published: 2014 Citation: Garay LA, Boundy-Mills KL, German JB. Accumulation of high-value lipids in single-cell microorganisms: a mechanistic approach and future perspectives. J Agric Food Chem. 2014 Apr 2;62(13):2709-27.
  • Type: Journal Articles Status: Published Year Published: 2014 Citation: Hosseini SM, Hosseini H, Mohammadifar MA, German JB, Mortazavian AM, Mohammadi A, Khosravi-Darani K, Shojaee-Aliabadi S, Khaksar R. Preparation and characterization of alginate and alginate-resistant starch microparticles containing nisin. Carbohydr Polym. 2014 Mar 15;103:573-80.
  • Type: Journal Articles Status: Published Year Published: 2014 Citation: Hallam MC, Barile D, Meyrand M, German JB, Reimer RA. Maternal high protein or prebiotic fiber diets affect maternal milk composition and gut microbiota in rat dams and their offspring. Obesity (Silver Spring). 2014 Jul 24. doi: 10.1002/oby.20849.
  • Type: Journal Articles Status: Published Year Published: 2014 Citation: Joslin AC, Green R, German JB, Lange MC. Concept mapping One-Carbon Metabolism to model future ontologies for nutrient-gene-phenotype interactions. Genes Nutr. 2014 Sep;9(5):419. doi: 10.1007/s12263-014-0419-1. Epub 2014 Aug 5.
  • Type: Journal Articles Status: Published Year Published: 2014 Citation: Sitepu IR, Garay LA, Sestric R, Levin D, Block DE, German JB, Boundy-Mills KL. Oleaginous yeasts for biodiesel: Current and future trends in biology and production. Biotechnol Adv. 2014 Nov 15;32(7):1336-1360. doi: 10.1016/j.biotechadv.2014.08.003. Epub 2014 Aug 27. Review.
  • Type: Journal Articles Status: Published Year Published: 2014 Citation: Guerrero A, Dallas DC, Contreras S, Chee S, Parker EA, Sun X, Dimapasoc L, Barile D, German JB, Lebrilla CB. Mechanistic Peptidomics: Factors that Dictate the Specificity on the Formation of Endogenous Peptides in Human Milk. Mol Cell Proteomics. 2014 Aug 29. pii: mcp.M113.036194
  • Type: Journal Articles Status: Published Year Published: 2014 Citation: Dashipour A, Razavilar V, Hosseini H, Shojaee-Aliabadi S, German JB, Ghanati K, Khakpour M, Khaksar R. Antioxidant and antimicrobial carboxymethyl cellulose films containing Zataria multiflora essential oil Int J Biol Macromol. 2014 Sep 16;72C:606-613.
  • Type: Journal Articles Status: Published Year Published: 2014 Citation: Dallas DC, Weinborn V, de Moura Bell JM, Wang M, Parker EA, Guerrero A, Hettinga KA, Lebrilla CB, German JB, Barile D. Comprehensive peptidomic and glycomic evaluation reveals that sweet whey permeate from colostrum is a source of milk protein-derived peptides and oligosaccharides. Food Res Int. 2014 Sep 1;63(Pt B):203-209.


Progress 01/01/13 to 09/30/13

Outputs
Target Audience: The target audience of the research includes scientists, policy makers and the food and health industries. We have used various mechanisms to reach this audience including published articles, presentations, conferences and media. We organized 3 conferences: the International Milk Genomics Consortium Project dedicated to assembling the genes responsible for lactation in a broad range of mammals hosted the 10th annual meeting of the consortium at UCDavis October 1-4 2013 with 100 scientists and industry representatives from around the world. The first conference on Mucosal Health was hosted at UC Davis September 30 2013 with 120 attendees for a one day event. The first International conference on human milk science and innovation was co-organized with Prolacta Biosciences and attracted 50 attendees in Los Angeles November 17-18 2013. Additional presentations during this period are listed below. German JB Milk, from Genomics to Function, what does it teach us about nourishment? In Milk and Lactation: Defining and Refining the Critical Questions Denver Colorado 2012 German JB invited lecture ‘Personalizing diet and health – opportunities for agricultural innovation’ Bio-Innovates Biosolutions for Agriculture, Alberta Canada German JB invited lecture ‘What can Evolution teach us about diet and Health’ The Discovery Center for Science & Technology, Los Angeles California invited lecture: German JB Regulatory oversight of health assessment: the tyranny of outcome American Association for the Advancement of Science, Annual Meeting Vancouver Canada 2012 German JB Evolution, Milk and the Development of the Infant Microbiome. Institutes of Medicine Food Forum Conference on the Human Microbiome Washington DC 2012 German JB Workshop Workshop: Diet & Human Health: The inputs to Phenotype, from Genetics to Food choices co-organizer United States Department of Agriculture, Washington DC April 2012 German JB Lipid Oxidation: from Evolution to Genomics. American Oil Chemists Society Annual Meeting workshop Long Beach California 2012 German JB ‘Breakthroughs in Science that are changing Diet and Health’ International Prune Association Annual Meeting Davis California 2012 German JB ‘The lessons of Diet and Health from Lactation’ The Hebrew University of Jerusalem, invited lecture Israel June 2012 German JB ‘Pre and Probiotics for Premature Infants’ Israel Nutrition Week and the AODA Regional Conference Tel Aviv Israel 2012 German JB ‘Dietetics as the Clinicians of Health for the 21st century’ Israel Nutrition Week and the AODA Regional Conference Tel Aviv Israel 2012 German JB What 200 million years of evolution has produced in milk and lactation. Euroscience Open Forum Dublin Ireland 2012 German JB ‘Translational nutrition: integrating research, practice and policy Plenary Lecture The Nutrition Society Summer Meeting Belfast Ireland 2012 German JB “Diet, Health and Sustainability for the 21st Century” Symposium: Sustainable Development for the 21st Century:?The Role of the Modern University. University of California, Davis. 2012 German JB How will Personalization Change the Food and Health Industries? Benefiq 2012 Quebec City Canada German JB Future opportunities for milk Research International Milk Genomics Consortium Annual Meeting Wageningen the Netherlands 2012 German JB Milk as a model for targets of health and sustainability in a fast growing world population. World Dairy Summit Cape Town South Africa, 2012 German JB The future of Nutrition in a personalized health marketplace: science and technology development. Dried Plum Board Annual Meeting, Sacramento 2013 German JB Texas A & M University Evolutionary Nutrition: guiding research for personalized diets” invited lecture 2013 German JB Scientific and Regulatory needs for Yogurt Experimental Biology 2013 Boston invited lecture German JB Evolutionary Nutrition: Lactation as a guiding model. Autism Research Institute Annual Workshop Baltimore Maryland invited lecture 2013 German JB Lactation and milk as a model for personalizing health and disease prevention. Southern California IFT Meeting Disneyland invited lecture 2013 German JB The microbiome and human health California Dietetic Association Annual Meeting Santa Clara invited lecture 2013 German JB ‘Diet and Lipid Metabolism: its personal’ invited lecture Satellite Symposium for Conference Can Foods Change your Health Hong Kong China July 2013 German JB ‘New & Novel Developments in Knowledge & Management of Wellness and Nutrition: From Breast to Best’ Conference Can Foods Change your Health Hong Kong China July 2013 Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided? Four post-doctoral fellows have been trained during the period in various aspects of project design, management and execution. Angela Zivkovic was recruited to a faculty position at the University of California Davis and thus left the program. During this period 6 PhD students have been moving towards completion of the graduate degrees and during the period, David Dallas and Hyeyoung Lee both received their PhD’s from the program. They are now working on post-doctoral programs, both targeting academic careers. Twenty undergraduate students were trained in research and analysis techniques appropriate to the mission of the program including milk analysis, clinical study management and publication preparation. How have the results been disseminated to communities of interest? German JB Milk, from Genomics to Function, what does it teach us about nourishment? In Milk and Lactation: Defining and Refining the Critical Questions Denver Colorado 2012 German JB invited lecture ‘Personalizing diet and health – opportunities for agricultural innovation’ Bio-Innovates Biosolutions for Agriculture, Alberta Canada German JB invited lecture ‘What can Evolution teach us about diet and Health’ The Discovery Center for Science & Technology, Los Angeles California invited lecture: German JB Regulatory oversight of health assessment: the tyranny of outcome American Association for the Advancement of Science, Annual Meeting Vancouver Canada 2012 German JB Evolution, Milk and the Development of the Infant Microbiome. Institutes of Medicine Food Forum Conference on the Human Microbiome Washington DC 2012 German JB Workshop Workshop: Diet & Human Health: The inputs to Phenotype, from Genetics to Food choices co-organizer United States Department of Agriculture, Washington DC April 2012 German JB Lipid Oxidation: from Evolution to Genomics. American Oil Chemists Society Annual Meeting workshop Long Beach California 2012 German JB ‘Breakthroughs in Science that are changing Diet and Health’ International Prune Association Annual Meeting Davis California 2012 German JB ‘The lessons of Diet and Health from Lactation’ The Hebrew University of Jerusalem, invited lecture Israel June 2012 German JB ‘Pre and Probiotics for Premature Infants’ Israel Nutrition Week and the AODA Regional Conference Tel Aviv Israel 2012 German JB ‘Dietetics as the Clinicians of Health for the 21st century’ Israel Nutrition Week and the AODA Regional Conference Tel Aviv Israel 2012 German JB What 200 million years of evolution has produced in milk and lactation. Euroscience Open Forum Dublin Ireland 2012 German JB ‘Translational nutrition: integrating research, practice and policy Plenary Lecture The Nutrition Society Summer Meeting Belfast Ireland 2012 German JB “Diet, Health and Sustainability for the 21st Century” Symposium: Sustainable Development for the 21st Century:?The Role of the Modern University. University of California, Davis. 2012 German JB How will Personalization Change the Food and Health Industries? Benefiq 2012 Quebec City Canada German JB Future opportunities for milk Research International Milk Genomics Consortium Annual Meeting Wageningen the Netherlands 2012 German JB Milk as a model for targets of health and sustainability in a fast growing world population. World Dairy Summit Cape Town South Africa, 2012 2013 German JB The future of Nutrition in a personalized health marketplace: science and technology development. Dried Plum Board Annual Meeting, Sacramento 2013 German JB Texas A & M University Evolutionary Nutrition: guiding research for personalized diets” invited lecture 2013 German JB Scientific and Regulatory needs for Yogurt Experimental Biology 2013 Boston invited lecture German JB Evolutionary Nutrition: Lactation as a guiding model. Autism Research Institute Annual Workshop Baltimore Maryland invited lecture 2013 German JB Lactation and milk as a model for personalizing health and disease prevention. Southern California IFT Meeting Disneyland invited lecture 2013 German JB The microbiome and human health California Dietetic Association Annual Meeting Santa Clara invited lecture 2013 German JB ‘Diet and Lipid Metabolism: its personal’ invited lecture Satellite Symposium for Conference Can Foods Change your Health Hong Kong China July 2013 German JB ‘New & Novel Developments in Knowledge & Management of Wellness and Nutrition: From Breast to Best’ Conference Can Foods Change your Health Hong Kong China July 2013 German JB organizer, International Milk Genomics Consortium 10th Anniversary conference. Davis California 2013 http://milkgenomics.org/10th-international-symposium-on-milk-genomics-and-human-health/ German JB CHAMMP Symposium September 30 University of California Davis co-organizer http://phylogenomics.wordpress.com/2013/09/05/register-for-the-2013-chammp-symposium-at-uc-davis-w-keynote-by-jeffrey-gordon/ German JB ‘the Milk Metabolome: from composition to function’ West Coast Metabolomics Center invited lecture http://metabolomics.ucdavis.edu/courses-and-seminars/workshops-and-seminars University of California, Davis 2013 German JB co-organizer: First International Congress on Human Milk Science and Innovation. Los Angeles California 2013 German JB Milk: a model for health research in the 21st century in: First International Congress on Human Milk Science and Innovation. Los Angeles California What do you plan to do during the next reporting period to accomplish the goals? We will continued to develop scientific evidence publish results and their implications, report to the scientific community in person and patent components and technologies to provide commercialization opportunities as appropriate. We will continue to pursue funding from Federal and State agencies, industrial partners and appropriate foundations. We will leverage that funding to recruit, train and promote students, post-doctoral fellows and visiting scientists. Where no other translational agencies are possible we will consider launching new corporate entities as the commercial means to carry the scientific research findings into the marketplace to improve foods and human health.

Impacts
What was accomplished under these goals? We have continued to develop scientific evidence that non-essential nutrients, including components from milk and plant secondary compounds, are absorbed, metabolized and biologically-active towards metabolic and chemical processes in animals and humans. We have worked in parallel to understand how a specific subset of human metabolism—fatty acid biochemistry—is responsive to diet and how to alter dietary lipids to improve specific aspects of overall health The results of our research to understand lipid metabolism imply that alterations in food would be the most appropriate means to achieve targeted alterations in metabolism maximizing efficacy and safety, thus, we have also continued to build knowledge on the composition and functions of foods, in particular, the lipid components of foods. We have continued our active research area in milk. In truth, it is the biological value of milk that is most convincing that we shall find approaches to foods that will be truly supportive of health rather than curative of disease. Discovering the molecular basis of milk's nutritional values has demonstrated considerable success in providing a blueprint for all of nutrition's future directions. We already know that milk provides health benefits that, until very recently, were not speculated. Milk components that selectively stimulate and support the competitive growth of beneficial intestinal bacteria, protect the intestine from pathogens, protect the intestine from toxins and educate the host's immune system. Such a value is a vivid example of how milk goes beyond the provision of nutrients essential to life, and provides good health and the promise for enhanced quality of life.

Publications

  • Type: Journal Articles Status: Published Year Published: 2013 Citation: 18. De Leoz ML, Wu S, Strum JS, Ni�onuevo MR, Gaerlan SC, Mirmiran M, German JB, Mills DA, Lebrilla CB, Underwood MA A quantitative and comprehensive method to analyze human milk oligosaccharide structures in the urine and feces of infants. Anal Bioanal Chem. 2013 Mar 7. [Epub ahead of print]
  • Type: Journal Articles Status: Published Year Published: 2013 Citation: Smilowitz JT, Zivkovic AM, Wan YJ, Watkins SM, Nording ML, Hammock BD, German JB. Nutritional lipidomics: Molecular metabolism, analytics, and diagnostics. Mol Nutr Food Res. 2013 Aug;57(8):1319-35.
  • Type: Journal Articles Status: Published Year Published: 2013 Citation: Zivkovic AM, Yang J, Georgi K, Hegedus C, Nording ML, O'Sullivan A, German JB, Hogg RJ, Weiss RH, Bay C, Hammock BD. Serum oxylipin profiles in IgA nephropathy patients reflect kidney functional alterations. Metabolomics. 2012 Dec;8(6):1102-1113.
  • Type: Journal Articles Status: Published Year Published: 2013 Citation: Kim JH, An HJ, Garrido D, German JB, Lebrilla CB, Mills DA. Proteomic Analysis of Bifidobacterium longum subsp. infantis Reveals the Metabolic Insight on Consumption of Prebiotics and Host Glycans. PLoS One. 2013;8(2):e57535. doi: 10.1371/journal.pone.0057535. Epub 2013 Feb 26.
  • Type: Journal Articles Status: Published Year Published: 2013 Citation: 20. Dallas DC, Guerrero A, Khaldi N, Castillo PA, Martin WF, Smilowitz JT, Bevins CL, Barile D, German JB, Lebrilla CB. Extensive in vivo Human Milk Peptidomics Reveals Specific Proteolysis Yielding Protective Antimicrobial Peptides. J Proteome Res. 2013 Apr 24. [Epub ahead of print]
  • Type: Journal Articles Status: Published Year Published: 2013 Citation: Sitepu IR, Sestric R, Ignatia L, Levin D, German JB, Gillies LA, Almada LA, Boundy-Mills KL. Manipulation of culture conditions alters lipid content and fatty acid profiles of a wide variety of known and new oleaginous yeast species. Bioresour Technol. 2013 Sep;144:360-9. doi: 10.1016/j.biortech.2013.06.047. Epub 2013 Jun 28.
  • Type: Journal Articles Status: Published Year Published: 2013 Citation: Ruiz-Moyano S, Totten SM, Garrido D, Smilowitz JT, German JB, Lebrilla CB, Mills DA. Variation in consumption of human milk oligosaccharides by infant-gut associated strains of Bifidobacterium breve. Appl Environ Microbiol. 2013 Jul 26. [Epub ahead of print]
  • Type: Journal Articles Status: Published Year Published: 2013 Citation: Lemay DG, Pollard KS, Martin WF, Freeman Zadrowski C, Hernandez J, Korf I, German JB, Rijnkels M.From Genes to Milk: Genomic Organization and Epigenetic Regulation of the Mammary Transcriptome. PLoS One. 2013 Sep 26;8(9):e75030.
  • Type: Journal Articles Status: Published Year Published: 2013 Citation: Smilowitz JT, Totten SM, Huang J, Grapov D, Durham HA, Lammi-Keefe CJ, Lebrilla C, German JB. Human Milk Secretory Immunoglobulin A and Lactoferrin N-Glycans Are Altered in Women with Gestational Diabetes Mellitus. J Nutr. 2013 Sep 18. [Epub ahead of print] PMID: 24047700
  • Type: Journal Articles Status: Published Year Published: 2013 Citation: Smilowitz JT, O'Sullivan A, Barile D, German JB, L�nnerdal B, Slupsky CM. The Human Milk Metabolome Reveals Diverse Oligosaccharide Profiles. J Nutr. 2013 Sep 11. [Epub ahead of print] PMID: 24027187 [PubMed - as supplied by publisher]
  • Type: Journal Articles Status: Published Year Published: 2013 Citation: Lee H, German JB, Kjelden R, Lebrilla CB, Barile D. Quantitative Analysis of Gangliosides in Bovine Milk and Colostrum-Based Dairy Products by Ultrahigh Performance Liquid Chromatography-Tandem Mass Spectrometry. J Agric Food Chem. 2013 Sep 30. [Epub ahead of print] PMID: 24024650
  • Type: Journal Articles Status: Accepted Year Published: 2012 Citation: 1. Chichlowski M, De Lartigue G, German JB, Raybould HE, Mills DA. Bifidobacteria Isolated From Infants And Cultured On Human Milk Oligosaccharides Affect Intestinal Epithelial Function. J Pediatr Gastroenterol Nutr. 2012 Feb 29. [Epub ahead of print]
  • Type: Journal Articles Status: Accepted Year Published: 2012 Citation: 2. Barboza M, Pinzon J, Wickramasinghe S, Froehlich JW, Moeller I, Smilowitz JT, Ruhaak LR, Huang J, L�nnerdal B, German JB, Medrano JF, Weimer BC, Lebrilla CB. Glycosylation of human milk lactoferrin exhibits dynamic changes during early lactationenhancing its role in pathogenic bacteria-host interactions. Mol Cell Proteomics. 2012 Jan 19. [Epub ahead of print]
  • Type: Journal Articles Status: Published Year Published: 2012 Citation: 3. Hernandez MR, Towns EN, Moore J, Lee H, German JB, Lebrilla CB, Parikh AN, Land DP. Use of attenuated total reflectance Fourier transform infrared spectroscopy to study lactosylceramide and GD3 DMPC bilayers. Colloids Surf B Biointerfaces. 2012 Feb 10. [Epub ahead of print]
  • Type: Journal Articles Status: Published Year Published: 2012 Citation: Heinze CR, Hawkins MG, Gillies LA, Wu X, Walzem RL, German JB, Klasing KC. Effect of dietary omega-3 fatty acids on red blood cell lipid composition and plasma metabolites in the cockatiel, Nymphicus hollandicus. J Anim Sci. 2012 May 14. [Epub ahead of print]
  • Type: Journal Articles Status: Published Year Published: 2012 Citation: 6. Bordiga M, Travaglia F, Meyrand M, German JB, Lebrilla CB, Co�sson JD, Arlorio M, Barile D. Identification and characterization of complex bioactive oligosaccharides in white and red wine by a combination of mass spectrometry and gas chromatography. J Agric Food Chem. 2012 Apr 11;60(14):3700-7. Epub 2012 Mar 28.
  • Type: Journal Articles Status: Published Year Published: 2012 Citation: 7. Nwosu CC, Aldredge DL, Lee H, Lerno LA, Zivkovic AM, German JB, Lebrilla CB. Comparison of the human and bovine milk N-glycome via high-performance microfluidic chip liquid chromatography and tandem mass spectrometry. J Proteome Res. 2012 May 4;11(5):2912-24. Epub 2012 Apr 6.
  • Type: Journal Articles Status: Published Year Published: 2012 Citation: 8. Lee H, Lerno Jr LA, Choe Y, Chu CS, Gillies LA, Grimm R, Lebrilla CB, German JB. Multiple Precursor Ion Scanning of Gangliosides and Sulfatides with a Reverse-Phase Microfluidic Chip and Quadrupole Time-of-flight Mass Spectrometry. Anal Chem. 2012 Jul 17;84(14):5905-12.
  • Type: Journal Articles Status: Published Year Published: 2012 Citation: 5. Sundekilde UK, Barile D, Meyrand M, Poulsen NA, Larsen LB, Lebrilla CB, German JB, Bertram HC. Natural variability in bovine milk oligosaccharides from Danish Jersey and Holstein-Friesian breeds. J Agric Food Chem. 2012 Jun 20;60(24):6188-96.
  • Type: Journal Articles Status: Published Year Published: 2012 Citation: Hinde K and German JB Food in an evolutionary context: insights from mother's milk Jnl. Science of Food and Agriculture Article 2012 Aug 30;92(11):2219-23. online: 21 JUN 2012 DOI: 10.1002/jsfa.5720
  • Type: Journal Articles Status: Published Year Published: 2012 Citation: 10. Garrido D, Nwosu C, Ruiz-Moyano S, Aldredge D, German JB, Lebrilla CB, Mills DA. Endo-?-N-acetylglucosaminidases from infant-gut associated bifidobacteria release complex N-glycans from human milk glycoproteins. Mol Cell Proteomics. 2012 Sep;11(9):775-85.
  • Type: Journal Articles Status: Published Year Published: 2012 Citation: 11. Neville MC, Anderson SM, McManaman JL, Badger TM, Bunik M, Contractor N, Crume T, Dabelea D, Donovan SM, Forman N, Frank DN, Friedman JE, German JB, Goldman A, Hadsell D, Hambidge M, Hinde K, Horseman ND, Hovey RC, Janoff E, Krebs NF, Lebrilla CB, Lemay DG, Maclean PS, Meier P, Morrow AL, Neu J, Nommsen-Rivers LA, Raiten DJ, Rijnkels M, Seewaldt V, Shur BD, Vanhouten J, Williamson P. Lactation and Neonatal Nutrition: Defining and Refining the Critical Questions. J Mammary Gland Biol Neoplasia. 2012 Jul 1. [Epub ahead of print]
  • Type: Journal Articles Status: Published Year Published: 2012 Citation: Dallas DC, Martin WF, Hua S, German JB. Automated glycopeptide analysis--review of current state and future directions. Brief Bioinform. 2012 Jul 27. [Epub ahead of print]
  • Type: Journal Articles Status: Published Year Published: 2012 Citation: 13. Wu S, Salcedo J, Tang N, Waddell K, Grimm R, German JB, Lebrilla CB. Employment of tandem mass spectrometry for the accurate and specific identification of oligosaccharide structures. Anal Chem. 2012 Sep 4;84(17):7456-62. Epub 2012 Aug 21.
  • Type: Journal Articles Status: Published Year Published: 2012 Citation: Strum JS, Kim J, Wu S, De Leoz ML, Peacock K, Grimm R, German JB, Mills DA, Lebrilla CB. Identification and Accurate Quantitation of Biological Oligosaccharide Mixtures.Anal Chem. 2012 Aug 29. [Epub ahead of print]
  • Type: Journal Articles Status: Published Year Published: 2012 Citation: De Leoz ML, Gaerlan SC, Strum JS, Dimapasoc LM, Mirmiran M, Tancredi DJ, Smilowitz JT, Kalanetra KM, Mills DA, German JB, Lebrilla CB, Underwood MA. Lacto-N-Tetraose, Fucosylation, and Secretor Status Are Highly Variable in Human Milk Oligosaccharides From Women Delivering Preterm. J Proteome Res. 2012 Aug 28. [Epub ahead of print]
  • Type: Journal Articles Status: Published Year Published: 2012 Citation: Lemay DG, Martin WF, Hinrichs AS, Rijnkels M, German JB, Korf I, Pollard KS. G-NEST: a gene neighborhood scoring tool to identify co-conserved, co-expressed genes. BMC Bioinformatics. 2012 Sep 28;13(1):253.
  • Type: Journal Articles Status: Published Year Published: 2012 Citation: Totten SM, Zivkovic AM, Wu S, Ngyuen U, Freeman SL, Ruhaak LR, Darboe MK, German JB, Prentice AM, Lebrilla CB. Comprehensive profiles of human milk oligosaccharides yield highly sensitive and specific markers for determining secretor status in lactating mothers. J Proteome Res. 2012 Dec 7;11(12):6124-33. doi: 10.1021/pr300769g. Epub 2012 Nov 19.


Progress 01/01/12 to 12/31/12

Outputs
OUTPUTS: Ongoing studies continue to address the questions: how does the quantity and composition of dietary lipids affect human metabolism and how can the evolution of mammalian lactation guide the design of diets for infants and adults. The research has been successful in several key points and we are taking important steps to move the knowledge gained into modifications in the food supply and in tools for improving the choices of overall diets made by individuals in the population. Lectures have been presented at several National and International meetings: Denver Colorado, Alberta Canada Los Angeles California, the American Association for the Advancement of Science, Annual Meeting Vancouver Canada the USA. Institutes of Medicine Food Forum Conference on the Human Microbiome Washington DC, workshop co-organizer United States Department of Agriculture, Washington DC American Oil Chemists Society Annual Meeting workshop Long Beach California The Hebrew University of Jerusalem, invited lecture Israel Israel Nutrition Week and the AODA Regional Conference Tel Aviv Israel. Euroscience Open Forum Dublin Ireland The Nutrition Society Summer Meeting Belfast Ireland Benefiq Quebec City Canada, International Milk Genomics Consortium Annual Meeting Wageningen the Netherlands, World Dairy Summit Cape Town South Africa, 2012. We have sought and obtained support from NIH, the Gates Foundation, Dairy Research Institute and Abbott Pharmaceuticals. The project originally formed and continues to guide a multi-national collaboration of scientists to understand milk components, the Milk Genomics Consortium, using the tools of bioinformatics, analytical chemistry and new models of biological processes PARTICIPANTS: A graduate student Hyeyoung Lee completed her PhD on this project and published her work in the form of three manuscripts. She also presented her work at conferences at the University of California, Davis and is planning on presenting at International conferences in 2013. TARGET AUDIENCES: Not relevant to this project. PROJECT MODIFICATIONS: Not relevant to this project.

Impacts
Lipids are one of the major biomolecule classes in all living organisms and are typically a significant fraction of foods. Research in this laboratory and others has described the lipids in diets as highly bioactive components and when lipid intakes are imbalanced the consequences to health are deleterious to health. The research also points out that the effects of lipids in the diet are not the same in all people and thus the effects of lipids in the diet cannot be predicted without considering the individual consuming them. The same lipids are positive to the health of one individual, yet negative to the health of another. Dietary lipids will need an individualized approach to human health. The first step we have taken has been to assemble analytical tools to assess human metabolism. The goal of this research and its applications are to align each individual's metabolism to the compositions, formulations and biological properties of lipids in foods. In parallel we have been studying lactation and milk as an evolutionary model for lipid nourishment. Milk and Lactation are our molecular and mechanistic guides to the effect of diet on metabolism, immunity, physiology, even sensation. This strategic approach has required new tools to chemically analyze the lipids of milk and biological models of the responses to milk lipids. Our objectives are to understand how the principles of nourishment contained in milk can be applied to humans of all ages. During the past period we have developed methods to analyze lipids from milk and other foods, examined their effects on lipid metabolism in humans and animals and continued the process of annotating the structures and functions of complex conjugates in milk. Understanding which structures and what quantities of these molecules should be included in the diets of all ages remains the goal of the research program

Publications

  • Strum JS., J. Kim, S. Wu, ML. De Leoz, K. Peacock, R. Grimm, JB. German, DA. Mills, CB. Lebrilla. Identification and Accurate Quantitation of Biological Oligosaccharide Mixtures.Anal Chem. 2012 Aug 29. [Epub ahead of print]
  • De Leoz ML., SC. Gaerlan, JS. Strum, LM. Dimapasoc, M. Mirmiran, DJ. Tancredi, JT. Smilowitz, KM. Kalanetra, DA. Mills, JB. German, CB. Lebrilla, MA. Underwood. Lacto-N-Tetraose, Fucosylation, and Secretor Status Are Highly Variable in Human Milk Oligosaccharides From Women Delivering Preterm. J Proteome Res. 2012 Aug 28. [Epub ahead of print]
  • Lemay DG., WF. Martin, AS. Hinrichs, M. Rijnkels, JB. German, I. Korf, KS. Pollard. G-NEST: a gene neighborhood scoring tool to identify co-conserved, co-expressed genes. BMC Bioinformatics. 2012 Sep 28;13(1):253.
  • Chichlowski M., G. De Lartigue, JB. German, HE. Raybould, DA. Mills. Bifidobacteria Isolated From Infants And Cultured On Human Milk Oligosaccharides Affect Intestinal Epithelial Function. J Pediatr Gastroenterol Nutr. 2012 Feb 29. [Epub ahead of print]
  • Barboza M., J. Pinzon, S. Wickramasinghe, JW. Froehlich, I. Moeller, JT. Smilowitz, LR. Ruhaak, J. Huang, B. Lonnerdal, JB. German, JF. Medrano, BC. Weimer, CB. Lebrilla. Glycosylation of human milk lactoferrin exhibits dynamic changes during early lactationenhancing its role in pathogenic bacteria-host interactions. Mol Cell Proteomics. 2012 Jan 19. [Epub ahead of print]
  • Hernandez MR., EN. Towns, J. Moore, H. Lee, JB. German, CB. Lebrilla, AN. Parikh, DP. Land. Use of attenuated total reflectance Fourier transform infrared spectroscopy to study lactosylceramide and GD3 DMPC bilayers. Colloids Surf B Biointerfaces. 2012 Feb 10. [Epub ahead of print]
  • Heinze CR., MG. Hawkins, LA. Gillies, X. Wu, RL. Walzem, JB. German, KC. Klasing. Effect of dietary omega-3 fatty acids on red blood cell lipid composition and plasma metabolites in the cockatiel, Nymphicus hollandicus. J Anim Sci. 2012 May 14. [Epub ahead of print]
  • Sundekilde UK., D. Barile, M. Meyrand, NA. Poulsen, LB. Larsen, CB. Lebrilla, JB. German, HC. Bertram. Natural variability in bovine milk oligosaccharides from Danish Jersey and Holstein-Friesian breeds. J Agric Food Chem. 2012 Jun 20;60(24):6188-96.
  • Bordiga M., F. Travaglia, M. Meyrand, JB. German, CB. Lebrilla, JD. Coisson, M. Arlorio, D. Barile. Identification and characterization of complex bioactive oligosaccharides in white and red wine by a combination of mass spectrometry and gas chromatography. J Agric Food Chem. 2012 Apr. 11:60(14):3700-7. Epub 2012 Mar 28.
  • Nwosu CC, DL. Aldredge, H. Lee, LA. Lerno, AM. Zivkovic, JB. German, CB. Lebrilla. Comparison of the human and bovine milk N-glycome via high-performance microfluidic chip liquid chromatography and tandem mass spectrometry. J Proteome Res. 2012 May 4;11(5):2912-24. Epub 2012 Apr 6.
  • Lee H., LA. Lerno Jr, Y. Choe, CS. Chu, LA. Gillies, R. Grimm, CB. Lebrilla, JB. German. Multiple Precursor Ion Scanning of Gangliosides and Sulfatides with a Reverse-Phase Microfluidic Chip and Quadrupole Time-of-flight Mass Spectrometry. Anal Chem. 2012 Jul 17;84(14):5905-12.
  • Hinde K. and JB. German Food in an evolutionary context: insights from mother's milk Jnl. Science of Food and Agriculture Article 2012 Aug 30;92(11):2219-23. online: 21 JUN 2012 DOI: 10.1002/jsfa.5720
  • Garrido D., C. Nwosu, S. Ruiz-Moyano, D. Aldredge, JB. German, CB. Lebrilla, DA. Mills. Endo-β-N-acetylglucosaminidases from infant-gut associated bifidobacteria release complex N-glycans from human milk glycoproteins. Mol Cell Proteomics. 2012 Sep;11(9):775-85.
  • Neville MC., SM. Anderson, JL. McManaman, TM. Badger, M. Bunik, N. Contractor, T. Crume, D. Dabelea, SM. Donovan, N. Forman, DN. Frank, JE. Friedman, JB. German, A. Goldman, D. Hadsell, M. Hambidge, K. Hinde, ND. Horseman, RC. Hovey, E. Janoff, NF. Krebs, CB. Lebrilla, DG. Lemay, PS. Maclean, P. Meier, AL. Morrow, J. Neu, LA. Nommsen-Rivers, DJ. Raiten, M. Rijnkels, V. Seewaldt, BD. Shur, J. Vanhouten, P, Williamson. Lactation and Neonatal Nutrition: Defining and Refining the Critical Questions. J Mammary Gland Biol Neoplasia. 2012 Jul 1. [Epub ahead of print]
  • Dallas DC., WF. Martin, S. Hua, JB. German. Automated glycopeptide analysis--review of current state and future directions. Brief Bioinform. 2012 Jul 27. [Epub ahead of print]
  • Wu S., J. Salcedo, N. Tang, K. Waddell, R. Grimm, JB. German, CB. Lebrilla. Employment of tandem mass spectrometry for the accurate and specific identification of oligosaccharide structures. Anal Chem. 2012 Sep 4;84(17):7456-62. Epub 2012 Aug 21.


Progress 01/01/11 to 12/31/11

Outputs
OUTPUTS: Research studies continue to address the questions: how do dietary lipids alter the metabolic fluxes of humans and how can the evolutionary process of mammalian milks guide scientific research to improve human diets. This program has yielded important insights into human health and we have taken many approaches to disseminate the knowledge broadly. The research has led to two conclusions: that personalizing health measurements are critical to the success of overall health management and that the mechanisms by which human milk provides unique benefits to the health of infants are translatable to improving diets for the health of children and adults. Articles have been published in journals and media of particular interest to the food industry to alert the commercial food sector to the implications of a changing consumer expectation for their foods. Lectures have been presented at 14 different international meetings: Euro Lipid Fed Annual Meeting Rotterdam the Netherlands, Association of Mass Spectrometry to the Clinical Laboratory San Diego California, International Dairy Federation, Parma Italy, International Conference, Delivery of Functionality in Complex Food Systems, Guelph University, Guelph, Ontario Canada American Nutrition Society, Western Canadian Dairy Seminar, Alberta Canada, Russel Klein Sympoisum Ohio State University, International Ambassador's Club, Ottawa, Canada, American Chemical Society Annual meeting. Denver Colorado, Stanford Mass Spec Annual Users Meeting, Linus Pauling Conference Corvallis Oregon, University of Wageningen, Wageningen, The Netherlands, International Milk Genomics Consortium 8th Annual Meeting Melbourne Australia. News articles were published in the New York Times, Nature, Proceedings of the National Academy of Sciences, USA and California media outlets. Ongoing research funding has been obtained from the National Institutes of Health, USDA, and the US National Dairy Board, the Gates foundation, Abbott Pharmaceuticals and Unilever Inc. PARTICIPANTS: One graduate student has been actively pursuing a PhD degree while involved in this research. Hyeyoung Lee a graduate student in Agricultural Chemistry has been developing methods to rapidly analyze complex glycolipids in order to measure their structures and abundances in human plasma and milk. She has published on article during the period. TARGET AUDIENCES: Not relevant to this project. PROJECT MODIFICATIONS: Nothing significant to report during this reporting period.

Impacts
Lipids are present as natural components of all living organisms and form a significant portion of virtually all foods. These components are functionally, organoleptically and nutritionally active providing many of the distinct and desirable properties of many foods. Nutrition research in this laboratory and others has described the lipids in diets as highly bioactive components and when lipid intakes are imbalanced the consequences to health are potentially deleterious to a variety of health outcomes. Unfortunately, research has also shown that the effects of lipids in the diet are not uniform and effects of lipids in the diet cannot be accurately assigned without considering the individual consuming them. The same lipids are positive to the health of one individual, yet negative to the health of another. With this biological reality in mind we have been developing strategies to bring a more individualized approach to human diets and health. The first step is to assemble tools to assess variations in human metabolism. These measured variables can then be matched to the compositions, formulations and biological properties of lipids and foods. What to measure is important but not enough to achieve prevention. We have been developing lactation and milk as an evolutionary model for nourishment. Milk and Lactation are our molecular and mechanistic guides for how diet can influence metabolism, immunity, physiology, even sensation. This strategic approach to diet has required new tools to study the lipids of milk, models of the responses to milk lipids and the means to vary the composition of milk lipids. The complex lipids in milk are structured in unique ways and hence the nutritional functions of these structures are being actively pursued. The program has formed and continues to guide a multi-national collaboration of scientists to understand milk components, using tools of bioinformatics, analytical chemistry and new models of biological processes. The goals are to understand how the principles of nourishment contained in milk can be applied to humans of all ages. During the past period we have developed the analytical tools to describe the structures of complex glycolipids in milk and we are now studying how these lipids influence the endogenous microflora within infants. Understanding which structures and what quantities of these molecules should be included in the diets of all ages remains the goal of the research program.

Publications

  • Tao N, Wu S, Kim J, An HJ, Hinde K, Power M, Gagneux P, German JB, 2011. Lebrilla CB. Evolutionary Glycomics: Characterization of Milk Oligosaccharides in Primates.J Proteome Res. Epub ahead of print.
  • Laugero KD, Smilowitz JT, German JB, Jarcho MR, Mendoza SP, Bales KL. 2011. Plasma omega 3 polyunsaturated fatty acid status and monounsaturated fatty acids are altered by chronic social stress and predict endocrine responses to acute stress in titi monkeys. Prostaglandins Leukot Essent Fatty Acids. Mar-Apr;84(3-4):71-8.
  • Selmi C, Leung PS, Fischer L, German B, Yang CY, Kenny TP, Cysewski GR, Gershwin ME. 2011. The effects of Spirulina on anemia and immune function in senior citizens. Cell Mol Immunol. Jan 31. Epub ahead of print.
  • Sela DA, Li Y, Lerno L, Wu S, Marcobal AM, German JB, Chen X, Lebrilla CB, Mills DA. 2011. An infant-associated bacterial commensal utilizes breast milk sialyloligosaccharides. J Biol Chem. Feb 2. Epub ahead of print.
  • Tao N, Wu S, Kim J, An HJ, Hinde K, Power M, Gagneux P, German JB, Lebrilla CB. 2011. Evolutionary Glycomics: Characterization of Milk Oligosaccharides in Primates. J Proteome Res. Jan 10. Epub ahead of print.
  • Nwosu CC, Seipert R, Strum JS, Hua SS, An HJ, Zivkovic AM, German JB, Lebrilla CB. 2011. Simultaneous and Extensive Site-specific N- and O-Glycosylation Analysis in Protein Mixtures. J Proteome Res. Apr 6. Epub ahead of print.
  • Smilowitz JT, German JB, Zivkovic AM. 2010. Food Intake and Obesity: The Case of Fat. In: Montmayeur JP, le Coutre J, editors. Fat Detection: Taste, Texture, and Post Ingestive Effects. Boca Raton (FL): CRC Press; Chapter 22.
  • Oberbauer AM, German JB, Murray JD. Growth hormone enhances arachidonic Acid metabolites in a growth hormone transgenic mouse Lipids. 2011 Jun;46(6):495-504. Epub Mar 27.
  • Garrido D, Kim JH, German JB, Raybould HE, Mills DA. 2011. Oligosaccharide Binding Proteins from Bifidobacterium longum subsp. infantis Reveal a Preference for Host Glycans. PLoS One. 2011 Mar 15;6(3):e17315.
  • German JB. 2011. Dietary lipids from an evolutionary perspective: sources, structures and functions. Matern Child Nutr. Apr;7 Suppl 2:2-16.
  • Yakes EA, Arsenault JE, Islam MM, Ahmed T, German JB, Drake C, Hossain MB, Lewis BL, Rahman AS, Jamil KM, Brown KH. 2011. Dietary Intake of Polyunsaturated Fatty Acids Among Breast-feeding and Non-breast-feeding 24- to 48-month-old Children in Bangladesh. J Pediatr Gastroenterol Nutr. Mar;52(3):351-9.
  • Dallas DC, Martin WF, Strum JS, Zivkovic AM, Smilowitz JT, Underwood MA, Affolter M, Lebrilla CB, German JB. 2011. N-linked glycan profiling of mature human milk by high performance microfluidic chip liquid chroma-tography time-of-flight tandem mass spectrometry. J Agric Food Chem. Mar 9. Epub ahead of print.
  • Lee H, An HJ, Lerno LA Jr, German JB, Lebrilla CB. 2011. Rapid Profiling of Bovine and Human Milk Gangliosides by Matrix-Assisted Laser Desorption/Ionization Fourier Transform Ion Cyclotron Resonance Mass Spectrometry.Int J Mass Spectrom. Aug 15;305(2-3):138-150.
  • Rincon G, Islas-Trejo A, Castillo AR, Bauman DE, German BJ, Medrano JF. 2011. Polymorphisms in genes in the SREBP1 signalling pathway and SCD are associated with milk fatty acid composition in Holstein cattle. J Dairy Res. 2011 Nov 25:1-10. Epub ahead of print.
  • Froehlich JW, Barboza M, Chu C, Lerno LA, Clowers BH, Zivkovic AM, German JB, Lebrilla CB. 2011. Nano-LC-MS/MS of Glycopeptides Produced by Nonspecific Proteolysis Enables Rapid and Extensive Site-Specific Glycosylation Determination. Anal Chem. Jul 15;83(14):5541-7. Epub 2011 Jun 28.
  • German JB, Angela M. Zivkovic, David C. Dallas, and Jennifer T. 2011. Smilowitz Nutrigenomics and Personalized Diets: What Will They Mean for Food Annual Review, Food Science and Technology, Vol. 2: 97-123.
  • Chichlowski Maciej, J. Bruce German, Carlito B. Lebrilla, and David A. Mills. 2011. The Influence of Milk Oligosaccharides on Microbiota of Infants: Opportunities for Formulas Annual Review of Food Science and Technology, Vol. 2: 331-351.
  • Wickramasinghe S, Hua S, Rincon G, Islas-Trejo A, German JB, Lebrilla CB, 2011. Medrano JF Transcriptome Profiling of Bovine Milk Oligosaccharide Metabolism Genes Using RNA-Sequencing. PLoS One. Apr 25;6(4):e18895.
  • Hua S, Nwosu CC, Strum JS, Seipert RR, An HJ, Zivkovic AM, German JB, Lebrilla CB. 2011. Site-specific protein glycosylation analysis with glycan isomer differentiation Anal Bioanal Chem. Jun 8. Epub ahead of print.
  • Marcobal A, Barboza M, Sonnenburg ED, Pudlo N, Martens EC, Desai P, Lebrilla CB, Weimer BC, Mills DA, German JB, Sonnenburg JL. 2011. Bacteroides in the Infant Gut Consume Milk Oligosaccharides via Mucus-Utilization Pathways.Cell Host Microbe. Oct 26. Epub ahead of print.
  • McNiven EM, German JB, Slupsky CM. 2011. Analytical metabolomics: nutritional opportunities for personalized health.J Nutr Biochem. Nov;22(11):995-1002.
  • Smilowitz JT, Wiest MM, Teegarden D, Zemel MB, German JB, Van Loan MD. 2011. Dietary fat and not calcium supplementation or dairy product consumption is associated with changes in anthropometrics during a randomized, placebo-controlled energy-restriction trial.Nutr Metab (Lond). Oct 5;8:67.


Progress 01/01/10 to 12/31/10

Outputs
OUTPUTS: Research studies continue to address the questions: how do dietary lipids alter the metabolic fluxes of animals and humans and how can the evolutionary process of mammalian milks guide molecular and mechanistic insights to improve human diets. This research has yielded important implications to human health and we have taken various approaches to disseminate the knowledge broadly. The research has led to two conclusions: that personalizing health measurements are critical to the future of overall health management and that human milk provides unique benefits to the health of infants whose mechanisms of action are translatable to the health of children and adults. Articles have been published in journals and media of particular interest to the food industry to alert the commercial food sector to the implications of a changing consumer expectation for their foods. Lectures have been presented at 12 different international meetings: International Life Sciences Institute Annual Meeting Puerto Rico Metabolomics and More Munich Germany Malaysia Nutrition Society Kuala Lumpur American Oil Chemists Society Annual Meeting Phoenix Arizona, The Utrecht Group Meeting. Utrecht, The Netherlands Satellite Symposium at the ISSFAL Maastricht, the Netherlands, International Society for Research in Human Milk and Lactation, 15th Annual Meeting Lima, Peru, International Life Science Institute Argentina, 20th Anniversary Celebration. Buenos Aires Argentina FrieslandCampina Annual Meeting Friesland, the Netherlands Montreux Symposium on LC/MS Montreux, Switzerland, American Chemical Society California Section. News articles were published in the New York Times, Nature, Proceedings of the National Academy of Sciences, USA and California media outlets. Subsequent research funding was pursued with the National Institutes of Health, USDA, and the US National Dairy Board. PARTICIPANTS: One graduate student has been actively pursuing a PhD degree while involved in this research. Hyeyoung Lee a graduate student in Agricultural Chemistry has been developing methods to rapidly analyze complex glycolipids in order to measure their structures and abundances in human plasma and milk. She has published on article during the period. TARGET AUDIENCES: Not relevant to this project. PROJECT MODIFICATIONS: Nothing significant to report during this reporting period.

Impacts
Lipids are present as natural components of virtually all agricultural commodities and thus form a significant portion of virtually all foods. These components are neither functionally nor nutritionally inert but provide many of the distinct and desirable properties of many foods. Furthermore, nutrition research has identified the lipids in diets as among the most bioactive components and indications are that when lipid intakes are imbalanced the consequences to health are potentially deleterious. Our research focuses understanding the role of dietary lipids in health. Studies on various different humans have been convincing that the effects of lipids in the diet cannot be accurately assigned without considering the individual consuming them. That is, the same lipids are positive to the health of one individual, yet negative to the health of another. Thus, improving human health through altering the quantity and quality of lipids in the diet must be ostensibly personalized. Optimizing diets will require that the tools to assess variations in human metabolism are matched to the compositions, formulations and biological properties of lipids. We have also been using milk as an evolutionary model of a complete diet that has emerged through millennia of selective pressure on the processes of lactation. Milk and Lactation are our molecular and mechanistic guides for how diet can influence many aspects of metabolism. We have assembled various new tools to study the lipids of milk and human plasma, models of metabolic responses to dietary lipids and the various consequences on health of varying the composition of dietary fats. The complex lipids in milk are structured in unique ways and yet the nutritional functions of these structures are not understood. Our ongoing multi-national collaboration of scientists that we have assembled to understand these components, has been building and applying tools of bioinformatics, analytical chemistry and new models of biological processes to understand how the principles of nourishment contained in milk can be applied to humans of all ages. Studies continue to demonstrate that the structures of complex glycolipids in milk influence a wide variety of health and pathological processes especially with respect to the endogenous microflora within humans. Understanding which structures and what quantities of these molecules should be included in human diets remains the goal of the research program.

Publications

  • Luria A, Morisseau C, Tsai HJ, Yang J, Inceoglu B, De Taeye B, Watkins SM, Wiest MM, German JB, Hammock BD. 2009 Alteration in Plasma Testosterone Levels in Male Mice Lacking Soluble Epoxide Hydrolase Am J Physiol Endocrinol Metab. May 19: Aug;297(2):E375-83.
  • Zivkovic AM, Wiest MM, Nguyen U, Davis R, Watkins SM, German JB. 2009 Effects of sample handling and storage on quantitative lipid analysis in human serum, Metabolomics. Dec;5(4):507-516.
  • Barboza M, Sela DA, Pirim C, Locascio RG, Freeman SL, German JB, Mills DA, Lebrilla CB. 2009 Glycoprofiling bifidobacterial consumption of galacto-oligosaccharides by mass spectrometry reveals strain specific, preferential consumption of glycans. Appl Environ Microbiol Apr (4):7319-7325.
  • Barile D, Tao N, Lebrilla CB, Coisson JD, Arlorio M, German JB. 2009 Permeate from cheese whey ultrafiltration is a source of milk oligosaccharides. Int Dairy J. Sept 1;19(9):524-530.
  • Zivkovic, Angela M. German, J. Bruce Esfandiari, Farah and Charles H. 2009 Halsted Quantitative Lipid Metabolomic Changes in Alcoholic Micropigs With Fatty Liver Disease Alcoholism. Jan 21:Clinical and Experimental Research Volume 33(4):751-758.
  • Tao Nannan, Ochonicky, Karen L, German, J Bruce, Donovan, Sharon M and Lebrilla, Carlito B. 2010 Structural Determination and Daily Variations of Porcine Milk Oligosaccharides. J. Agric. Food Chem. 58(8):4653-4659.
  • Lerno LA Jr, German JB, Lebrilla CB. 2010 Method for the identification of lipid classes based on referenced Kendrick mass analysis. Anal Chem. May 15;82(10):4236-45.
  • Froehlich JW, Dodds ED, Barboza M, McJimpsey EL, Seipert RR, Francis J, An HJ, Freeman S, German JB, Lebrilla CB. 2010 Glycoprotein expression in human milk during lactation. J Agric Food Chem. May 26;58(10):6440-8.
  • Marcobal A, Barboza M, Froehlich JW, Block DE, German JB, Lebrilla CB, Mills DA. 2010 Consumption of human milk oligosaccharides by gut-related microbes. J Agric Food Chem. May 12;58(9):5334-40.
  • Freeman SL, Fisher L, German JB, Leung PS, Prince H, Selmi C, Naguwa SM, Gershwin ME. 2010 Dairy proteins and the response to pneumovax in senior citizens: a randomized, double-blind, placebo-controlled pilot study. Ann N Y Acad Sci. Mar;1190(1):97-103.
  • Wu S, Tao N, German JB, Grimm R, Lebrilla CB. 2010 The development of an annotated library of neutral human milk oligosaccharides. J Proteome Res. Jun 28:Epub ahead of print.
  • Barile D, Marotta M, Chu C, Mehra R, Grimm R, Lebrilla CB, German JB. 2010 Neutral and acidic oligosaccharides in Holstein-Friesian colostrum during the first 3 days of lactation measured by high performance liquid chromatography on a microfluidic chip and time-of-flight mass spectrometry. J Dairy Sci. Sept;93(9):3940-9.
  • Lee H, An HJ, Lerno LA, German JB and Lebrilla CB. 2010 Rapid profiling of bovine and human milk gangliosides by matrix-assisted laser desorption/ionization Fourier transform ion cyclotron resonance mass spectrometry. Int. J. Mass Spec. (in press)
  • Flores JD, Newsome R, Fisher W, Barbosa-Canovas GV, Chen H, Dunne CP, German JB, Hall RL, Heldman DR, Karwe MV, Knabel SJ, Labuza TP, Lund DB, Newell-McGloughlin M, Robinson JL, Sebranek JG, Shewfelt RL, Tracy WF, Weaver CM, Ziegler GR. 2010 Feeding the World Today and Tomorrow: The imporatnce of Food Science and Technology Comprehensive Reviews in Food Science and Food Safety. Sept;Volume 9(5):572-599.
  • Zivkovic AM, German JB, Lebrilla CB, Mills DA. 2010 Microbes and Health Sackler Colloquium: Human milk glycobiome and its impact on the infant gastrointestinal microbiota. Proc Natl Acad Sci U S A. Aug 4:Epub ahead of print.
  • Argov-Argaman N, Smilowitz JT, Bricarello DA, Barboza M, Lerno L, Froehlich JW, Lee H, Zivkovic AM, Lemay DG, Freeman S, Lebrilla CB, Parikh AN, German JB. 2010 Lactosomes: Structural and Compositional Classification of Unique Nanometer-Sized Protein Lipid Particles of Human Milk. J Agric Food Chem. 2010 Oct 6:Epub ahead of print.
  • Hagopian K, Weber KL, Hwee DT, Van Eenennaam AL, Lopez-Lluch G, Villalba JM, Buron I, Navas P, German JB, Watkins SM, Chen Y, Wei A, McDonald RB, Ramsey JJ. 2010 Complex I-associated hydrogen peroxide production is decreased and electron transport chain enzyme activities are altered in n-3 enriched fat-1 mice. PLoS One. Sept 13;5(9):e12696.
  • German JB and Dillard CJ. 2010 Saturated Fats: A Perspective from Lactation and Milk Composition. Lipids:Volume 45(10):915-923.
  • Baker AC, Mattos AD, Watkins S, German JB, Troppmann C, Perez R. 2010 Pretransplant Free Fatty Acids (FFA) and Allograft Survival in Renal Transplantation. J Surg Res. Aug 17:Epub ahead of print.
  • Bricarello DA, Smilowitz JT, Zivkovic AM, German JB, Parikh AN. 2010 Reconstituted Lipoprotein: A Versatile Class of Biologically-Inspired Nanostructures. ACS Nano. Dec 23:Epub ahead of print.


Progress 01/01/09 to 12/31/09

Outputs
OUTPUTS: Research studies address the question: how do dietary lipids alter the metabolic fluxes of animals and humans and how can the evolutionary process of mammalian milks guide molecular and mechanistic insights into novel strategies to improve human diets. Studies in 2009 investigated the implications of dietary lipids on dynamic metabolic pathways following the ingestion of a standardized meal (Zivkovic et al., 2009, Smilowitz et al., 2009, Zivkovic and German 2009). Studies have continued to address the distinctions between trans fatty acids produced by industrial hydrogenation versus those produced in the bovine rumen (Locke et al., 2009). We have investigated the importance of omega 3 metabolism to the survival of the well described animal model c. elegans (Hilyard and German 2009). The implications of these studies on animal models have led to the measurement of differences in different lipid metabolites in various health conditions and found that children with autism have slight but potentially important differences in the abundance of long chain polyunsaturated fatty acids of the omega 3 family (Weist et al., 2009). The components of milk remain poorly measured and annotated. Research has been establishing the tools to measure and understand the functions of oligosaccharides, proteins and lipids of milk (Loacscio et al., 2009, Dodds et al., 2009 Tao et al., 2009, German et al., 2009). The ongoing research initiatives to develop tools to understand the emergence of lactation in mammalia has led to a significant role in the Bovine Genome sequence project (Lemay et al., 2009, Elsink et al., 2009). Research is continuing to develop these new tools of analytical chemistry, biochemistry, metabolism and bioinformatics to provide the basic scientific understanding necessary to individualize human health measurments and personalize human diets (Watzke and German 2009, Bier et al., 2009). PARTICIPANTS: Nothing significant to report during this reporting period. TARGET AUDIENCES: Nothing significant to report during this reporting period. PROJECT MODIFICATIONS: Nothing significant to report during this reporting period.

Impacts
Lipids as visible ingredients (i.e. fats and oils) or as natural components of commodities form a vital portion of virtually all foods. These components provide many of the distinct and desirable properties of many foods. Furthermore, nutrition research has recognized that the lipids in diets are among the most bioactive components and particularly when lipid intakes are imbalanced the consequences to health are potentially deleterious. Our research focuses on the basic biological reality that the role of dietary lipids in health cannot be assigned without considering the individual consuming them. That is, the same lipids are positive to the health of one individual, yet negative to the health of another. Thus, improving human health through better diets will require that the tools to assess variations in human metabolism are matched to the compositions, formulations and biological properties of lipids. Milk is an evolutionary model of the emergence of a complete diet through the processes of lactation and is our molecular and mechanistic guide for how diet can influence many aspects of metabolism. In the past year we have discovered that the subset of the lactation genome that is most conserved throughout mammalia is in fact, the lipids. At the opposite side of this evolutionary spectrum, oligosaccharides have been increasing in their complexity and abundance in recent mammals and particularly humans. The lipids and the oligosaccharides in milk are structured in unique ways and yet the nutritional functions of these structures are not understood. The multi-national collaboration of scientists that we have assembled to understand these components, has been building and applying tools of bioinformatics, analytical chemistry and new models of biological processes to understand how the principles of nourishment contained in milk can be applied to humans of all ages. These molecules provide unique nutritional values, and the immediate goals are to understand which structures are responsible. Once the structures are known, we shall pursue methods to industrialize their production.

Publications

  • Locascio R.G., Ninonuevo M.R., Freeman S.L., Sela D.A., Grimm R., Lebrilla C.B., Mills D.A., German J.B. Glycoprofiling of Bifidobacterial Consumption of Human Milk Oligosaccharides Demonstrates Strain Specific, Preferential Consumption of Small Chain Glycans Secreted in Early Human Lactation. J. Ag. Food Chem. 2007 Oct 31; 55(22):8914-9.
  • Elsink C.G., Tellam R.L., Wolsey K.C. et al., The Genome Sequence of Taurine Cattle: A window to ruminant biology and evolution Science Science. 2009 Apr 24;324(5926):522-8.
  • Zivkovic A.M. Wiest M.M., Nguyen U., Nording M.L. Watkins S.M., German J.B. Assessing individual metabolic responsiveness to a lipid challenge using a targeted metabolomic approach Metabolomics 5 2009 (in press).
  • Dodds E.D., Seipert R.R., Clowers B.H., German J.B., Lebrilla C.B. Analytical Performance of Immobilized Pronase for Glycopeptide Footprinting and Implications for Surpassing Reductionist Glycoproteomics. J Proteome Res. 2009 Dec 11. [Epub ahead of print].
  • Bier D.D., Derilian D. German, J.B. Katz D.L., Pate R.R.; Thompson, K.M. Improving Compliance With Dietary Recommendations: Time for New, Inventive Approaches DM Nutrition Today:Volume 43(5)September/October 2008 pp 180-187. Lock A.L., Destaillats F., Kraft J., German J.B. Introduction to the proceedings of the symposium "Scientific Update on Dairy Fats and Cardiovascular Diseases". J Am Coll Nutr. 2008 Dec;27(6):720S-2S.
  • German J.B., Gibson R.A., Krauss R.M., Nestel P., Lamarche B., van Staveren W.A., Steijns J.M., de Groot L.C., Lock A.L., Destaillats F.A. reappraisal of the impact of dairy foods and milk fat on cardiovascular disease risk. Eur J Nutr. 2009 Mar 4. [Epub ahead of print].
  • Hillyard S.L., German J.B. Quantitative Lipid Analysis and Life Span of the fat-3 Mutant of Caenorhabditis elegans. J Agric Food Chem. 2009 Apr 22;57(8):3389-96.
  • Wiest M.M., German J.B., Harvey D.J., Watkins S.M., Hertz-Picciotto I. Plasma fatty acid profiles in autism: A case-control study. Prostaglandins Leukot Essent Fatty Acids. 2009 Mar 21. [Epub ahead of print].
  • Lemay D.G., Rijnkels M., German J.B. Lessons from the bovine genome: implications for human nutrition and research. J Nutr. 2009 Jul;139(7):1271-2.
  • Watzke H.J. and German J.B. Personalizing Foods in An Integrated Approach to New Food Product Development chapter Eds Saguy and 9 pp 134-174 Zivkovic A.M., German J.B. Metabolomics for assessment of nutritional status. Curr Opin Clin Nutr Metab Care. 2009 Jul 3. [Epub ahead of print] Tao N., DePeters E.J., German J.B., Grimm R., Lebrilla C.B. Variations in bovine milk oligosaccharides during early and middle lactation stages analyzed by high-performance liquid chromatography-chip/mass spectrometry. J Dairy Sci. 2009 Jul;92(7):2991-3001.


Progress 01/01/08 to 12/31/08

Outputs
OUTPUTS: Research continues to understand how dietary lipids alter the metabolic fluxes of animals and humans and how the evolutionary process of mammalian milks provides molecular and mechanistic insights into novel strategies to improve human diets. Studies in 2008 continued to examine the implications of dietary lipids on metabolic diseases (Astle et al., Fay, L-B and German, Chardigny et al,German). Studies have examined the distinctions between trans fatty acids produced by industrial hydrogenation versus those produced in the bovine rumen (Chardigny et al). We have continued to examine the role of food structure on its nutritional properties and discovered a small lipid particle class that is abundant in mammalian milks but heretofore largely ignored due to its small size (Argov et al, Argov et al). The consequences of undigestible components in milk to alter the intestinal microflora constitutes a new area of active research in the program with studies to date finding remarkably unique structures of undigestible oligosaccharides in human breast milk (Dodds et al, Ninonuevo et al., German et al, Seipert et al,Tao et al., Sela et al). The new fields of nutrigenomics and metabolomics are providing considerable opportunities to assess human health and guide diets to specific individuals (Astle et al., Fay, L-B and German, German). Nonetheless, the opportunities possible with these new tools cannot be fully achieved without a considerable investment in building the critical databases needed and making these available to the entire scientific community as standardized, public datasets (Lemay et al). Research is continuing to develop these new tools of bioinformatics and provide examples of their appropriate applications to food and nutrition research. PARTICIPANTS: Nothing significant to report during this reporting period. TARGET AUDIENCES: Nothing significant to report during this reporting period. PROJECT MODIFICATIONS: Nothing significant to report during this reporting period.

Impacts
Lipids (i.e. fats and oils) in foods either naturally or due to industrial design and formulations provide many of the distinct and desirable properties of many foods. Nonetheless, ongoing nutrition research has recognized that diets imbalanced in lipids are potentially deleterious to the health of individual humans. It is not yet certain which dietary fats are deleterious and those that are beneficial, nor for whom. Improving human health through better diets will require that the tools to assess variations in human metabolism are matched to the disparate health properties of lipids and to understand simultaneously their benefits and liabilities. Milk is a model of how diet can influence many aspects of metabolism. Milk is rich in various components including complex lipids and mammalian milks provide models to understand how components in the diet would be beneficial from a health perspective. Ongoing studies of human milk have continued to reveal biological strategies for nourishing humans that are not apparent in examining simple plant foods. For example the oligosaccharides that are abundant in human milk are unique in their structures and functions. The lipids in milk are structured in unique ways and yet the nutritional functions of these structures are not understood. Having assembled a multi-national collaboration of scientists to understand these components, we have begun apply new tools of bioinformatics, analytical chemistry and new models of biological processes to understand how the principles of nourishment contained in milk can be applied to humans of all ages. These molecules provide unique nutritional values, and the immediate goals are to understand which structures are responsible. Once the structures are known, we shall pursue methods to industrialize their production.

Publications

  • German JB. 2008 Looking into the future of foods and health. Innovation: Management, Policy Practice, 10 (1) 109-121
  • Argov N. Lemay D.G. and German JB 2008 Milk fat globule structure and function: nanoscience comes to milk production Trends in Food Science & Technology 19, 12, 617-623
  • Tao N, DePeters EJ, Freeman S, German JB, Grimm R, Lebrilla CB. Tao N, DePeters EJ, Freeman S, German JB, Grimm R, Lebrilla CB. 2008 The Bovine Glycome J Dairy Sci. Oct;91(10):3768-78.
  • Sela David A. Chapman J., Adeuya A., Kim J.H., Chen F., Whitehead T.R., Lapidus A., Rokhsar D.S., Lebrilla C.B., German J.B, Price N.P., Richardson P.M Mills D.A. 2008 The Complete Genome Sequence of Bifidobacterium longum subsp. infantis Reveals Adaptations for Milk Utilization within the Infant Microbiome Proceedings of the National Academy USA Dec 2;105(48):18964-9
  • Astle J, Ferguson JT, German JB, Harrigan GG, Kelleher NL, Kodadek T, Parks BA, Roth MJ, Singletary KW, Wenger CD, Mahady GB. 2007. Characterization of Proteomic and Metabolomic Responses to Dietary Factors and Supplements. J Nutr. Dec;137(12):2787-2793.
  • Dodds ED, German JB, Lebrilla CB. 2007 Enabling MALDI-FTICR-MS/MS for High-Performance Proteomics through Combination of Infrared and Collisional Activation. Anal Chem. Nov 15; epub
  • Lemay DG, Neville MC, Rudolph MC, Pollard KS, and German JB. 2007 Gene regulatory networks in lactation: identification of global principles using bioinformatics BMC Systems Biology. Nov 27;1:56.
  • Ninonuevo, M. R.; Perkins, P. D.; Francis, J.; Lamotte, L.; LoCascio, R.G.; German, J. B.; Freeman, S. L.; Grimm, R.; Lebrilla, C. B. 2008 Daily variations in oligosaccharides of human milk determined by microfluidic chips and mass spectrometry. J Agric Food Chem. Jun 25;56(12):4854.
  • Fay, L-B and German JB 2008 Personalizing foods: is genotype necessary Curr Opin Biotechnol. Apr;19(2):121-8
  • German JB, Freeman SL, Lebrilla CB, Mills DA. 2008 Human milk oligosaccharides: evolution, structures and bioselectivity as substrates for intestinal bacteria. Nestle Nutr Workshop Ser Pediatr Program. 62:205-22.
  • Seipert RR, Dodds ED, Clowers BH, Beecroft SM, German JB, Lebrilla CB. 2008 Factors that influence fragmentation behavior of N-linked glycopeptide ions. Anal Chem. May 15;80(10):3684-92
  • Chardigny JM, Destaillats F, Malpuech-Brugere C, Moulin J, Bauman DE, Lock AL, Barbano DM, Mensink RP, Bezelgues JB, Chaumont P, Combe N, Cristiani I, Joffre F, German JB, Dionisi F, Boirie Y, Sebedio JL. 2008 Do trans fatty acids from industrially produced sources and from natural sources have the same effect on cardiovascular disease risk factors in healthy subjects Results of the trans Fatty Acids Collaboration (TRANSFACT) study. Am J Clin Nutr. Mar;87(3):558-66.
  • Argov N, Wachsmann-Hogiu S, Freeman SL, Huser T, Lebrilla CB, German JB. 2008 Size-Dependent Lipid Content in Human Milk Fat Globules. J Agric Food Chem. Jul 26. Aug 27;56(16):7446-50


Progress 01/01/07 to 12/31/07

Outputs
Research continues to understand how dietary lipids alter the metabolic fluxes of animals and humans and how the evolutionary process of mammalian milks provides molecular and mechanistic insights into novel strategies to improve human diets (Hilyard and German, Frankel and German). Studies in 2007 focused on the implications of dietary lipids on metabolic diseases (Zivkovic and German, Zivkovic et al., German et al.). Studies have examined the distinctions between trans fatty acids produced by industrial hydrogenation versus those produced in the bovine rumen (Destaillats et al.). We have continued to examine the role of food structure on its nutritional properties and found that milk is a remarkably structuring food material with considerable delaying of intestinal clearance accomplished by self-assembling structures (Lemay Dillard & German). The consequences of undigestible components in milk to alter the intestinal microflora constitutes a new area of active research in the program with studies to date finding remarkably unique structures of undigestible oligosaccharides in human breast milk (Ninonueva et al., Ward et al., Locascio et al., Seipert et al.). The new fields of nutrigenomics and metabolomics are providing considerable opportunities to assess human health and guide diets to specific individuals (German & Watzke, Lange et al.). Nonetheless, the opportunities possible with these new tools cannot be fully achieved without a considerable investment in building the critical databases needed and making these available to the entire scientific community as standardized, public datasets (Lemay et al). Research is continuing to develop these new tools of bioinformatics and provide examples of their appropriate applications to food and nutrition research.

Impacts
Lipids (i.e. fats and oils) in foods either naturally or due to explicit formulations provide many of the distinct and desirable properties of many foods, though ongoing nutrition research has recognized that diets imbalanced in lipids are potentially highly deleterious to the health of individuals. However, it is not yet certain which dietary fats are deleterious nor for whom. Thus dietary guidelines recommend to limit the consumption of dietary fat without considerable information beyond a simple lower fat diet. Improving human health through better diets will require that the tools to assess variations in human health are matched to the disparate health properties of lipids and to understand simultaneously their benefits and liabilities. Milk is a model of how diet can influence many aspects of metabolism and mammalian milks provide models of various lactation strategies to understand which components in the diet would be optimum from a health perspective. Ongoing studies of human milk have continued to reveal biological strategies for nourishing humans that are not apparent in examining simple plant foods. For example the oligosaccharides that are abundant in human milk are unique in their structures and functions. Having assembled a multi-national collaboration of scientists to understand these components, we have begun apply new tools of bioinformatics, analytical chemistry and new models of biological processes to understand how the principles of nourishment contained in milk can be applied to humans of all ages. These molecules provide unique nutritional values, and the immediate goals are to understand which structures are responsible. Once the structures are known, we shall pursue methods to industrialize their production.

Publications

  • Lemay D. Dillard C.J. and German J.B. 2006 Nutrition and Food Structure in Food Colloids Self-Assembly and Material Science. editor Eric Dickinson and Martin Leser pub Royal Society of Chemistry London UK
  • Frankel EN and German JB. 2006 Antioxidants in foods and health: problems and fallacies in the field J. Sci. Food Ag. 8.13.v 1999-2001
  • Ninonuevo M.R., Ward R.E., LoCascio R.G., German J.B., Freeman S.L, Barboza M, Mills D.A. and Lebrilla C.B. 2007 Methods for the quantitation of human milk oligosaccharides in bacterial fermentation by mass spectrometry. Analytical Biochemistry 361, 15-23
  • German JB and Watzke H., 2007 The Future of Food in Personalized Nutrition eds Frans Kok, Laura Bouwman & Frank Dessiere. CRC Press Boca Raton FL pp261-279
  • Lange M. C., D. A. Lemay and J. B. German. 2007 Multi-ontology framework to guide agriculture and food toward diet and health, J. Sci. Food Agric. Volume 87, Issue 8, Date: June 2007, Pages: 1427-1434.
  • Zivkovic A. M., and J.B., German. 2007 Individual variation in the metabolic syndrome: anew perspective on the debate. American Journal of Clinical Nutrition letter to the editor 85(1) 240-241
  • German JB, Gillies LA, Smilowitz JT, Zivkovic AM, Watkins SM. 2007 Lipidomics and lipid profiling in metabolomics. Curr Opin Lipidol. Feb;18(1):66-71.
  • Hillyard S.L. and German JB. 2007 None-essential dietary factors: from test tube to lifespan. J. Sci. Food & Ag. 87 Volume 87, Issue 10, Pages: 1802-1805
  • Zivkovic AM, German JB, Sanyal AJ. 2007 Comparative review of diets for the metabolic syndrome: implications for nonalcoholic fatty liver disease. Am J Clin Nutr. 86(2):285-300.
  • Locascio RG, Ninonuevo MR., Freeman SL., Sela DA., Grimm R, Lebrilla CB., Mills DA., German JB. 2007 Glycoprofiling of Bifidobacterial Consumption of Human Milk Oligosaccharides Demonstrates Strain Specific, Preferential Consumption of Small Chain Glycans Secreted in Early Human Lactation. J. Ag. Food Chem. 55(22):8914-9.
  • Ward Robert E., Milady Ninonuevo, David A. Mills, Carlito B. Lebrilla J. Bruce German. 2007 In vitro fermentability of human milk oligosaccharides by several strains of bifidobacteria Mol. Nutr. Food Res. 51(11):1398-405.
  • Destaillats F. et al., 2008 Do Industrially-Produced and Natural Tans-Fatty acid Sources have the same impact on Cardiovascular Disease Risk Factors in Healthy Subjects? Results of the Transfact study. Am J. Clin Nutr. (in press)
  • Lemay DG, Zivkovic AG and German JB 2007 Building the Bridges to Bioinformatics in Nutrition Research. Am J Clin Nutr. 86: 1261
  • Seipert, R; Barboza, M; Ninonuevo, M; LoCascio, R; Mills, D; Freeman, S; German, JB.; Lebrilla, C. 2007 Analysis and Quantitation of Fructooligosaccharides using Matrix-Assisted Laser Desorption/Ionization Fourier Transform Ion Cyclotron Resonance Mass Spectrometry J. Ag. Food Chem. 80(1); 159-165.


Progress 01/01/06 to 12/31/06

Outputs
Research continues to understand how dietary lipids alter the metabolic fluxes of animals and humans and how the evolutionary process of mammalian milks provides molecular and mechanistic insights into novel strategies to improve human diets. Studies have focused in 2006 on the consequences of consuming milk lipids. The lipids of milk are not naturally a simple protein stabilized globule of triglycerides as is produced during homogenization. Rather, the globule structure is a remarkable cocktail of complex lipids including a conspicuous abundance of membrane phospholipids (Ward et al). The implications of the structures and compositions of natural fat globules have not been studied in any detail and thus we have begun to explore the implications of the actual structures of native fat globules. The diversity of fatty acids in milk have not been thoroughly considered either (German and Dillard). The increasing attention of scientists, regulatory agencies and the food industry on trans fats has largely ignored the fact that there is a fundamental chemical difference between naturally occurring trans found in ruminants (bovine meat, milk and dairy products) and the trans fats produced by industrial hydrogenation. A large multi-center trial has been started to understand the metabolic and health consequences of these chemical differences (Chardigny et al.). Perhaps most surprisingly, as the tools of nanoscience have gained widespread acceptance as being a powerful new scientific field, the most critically important nanoparticles in human health; serum lipoproteins, have been ignored in the rush to invent and describe completely novel nano-materials. We have addressed the opportunities available to these two scientific communities if they refocused the attention of nanoscience on biological particles that are of larger impact to the foreseeable future of science based technologies (German et al.). In part to understand the metabolic consequences of consuming lipids and also because metabolic disregulation continues to grow as a threat to health the technologies used to measure metabolism in a comprehensive and accurate manner remain a priority (German et al, Ninonuevo et al). Consensus for how to proceed in the new fields of nutrigenomics and metabolomics particularly as they relate to diet and health is being assembled and published as position documents (Dixon et al). The establishment of the International Milk Genomics Consortium represents a breakthrough in building an International team of scientists to address the multi-disciplinary task of understanding the health implications of mammalian milks (German et al.). Ongoing research under this umbrella is establishing new tools of bioinformatics that are necessary to building a knowledge base that is both accessible to a wide audience of scientists and strategically valuable in guiding cross-disciplinary and collaborative research on milk.

Impacts
The lipids (i.e. fats and oils) are responsible for many of the distinct and desirable organoleptic properties of many foods, yet nutrition research suggests that fats in foods may be deleterious and the dietary guidelines recommend to limit the consumption of dietary fat. To improve the overall quality of foods and diets, it is necessary to reconcile these disparate properties of lipids, to build an integrated view of the lipids in agricultural commodities and foods and to understand simultaneously their benefits and liabilities. Milk is a model of how diet can influence many aspects of metabolism and mammalian milks provide models of various lactation strategies to understand which components in the diet would be optimum from a health perspective. In studying human milk we have been struck by the complexity of the molecules contained therein and the discouraging lack of scientific knowledge of the evolutionary selective advantages that led to them being there. The oligosaccharides are abundant in human milk but it is still not known why. We have established a large multi-national collaboration of scientists to understand these components. We have begun to develop the tools that all scientists can use to address the many questions that the presence of these metabolites in milk pose. If these molecules provide unique nutritional values, then it is critical to know which structures are responsible. Finally we are pursuing the structure/function relationships of these materials to be able to produce them industrially and make them available to the entire food supply.

Publications

  • Ward, Robert E. Milady Ninonuevo, David A. Mills, Carlito B. Lebrilla, and J. Bruce German (2006) In Vitro Fermentation of Breast Milk Oligosaccharides by Bifidobacterium infantis and Lactobacillus gasseri Appl. Environ. Microbiol. 2006 72: 4497-4499.
  • Dixon RA, Gang DR, Charlton AJ, Fiehn O, Kuiper HA, Reynolds TL, Tjeerdema RS, Jeffery EH, German JB, Ridley WP, Seiber JN. Applications of Metabolomics in Agriculture. J Agric Food Chem. 2006 Nov 29;54(24):8984-8994.
  • German J.B. Smilowitz J. and Zivkovic A. (2006) Lipoproteins: when size really matters. Current Opinion in Colloid and Interfacial Science 2006 11; 171-183.
  • German JB, Dillard CJ, Hillyard SL, Lange MC, Smilowitz JT, Ward RE, Zivkovic AM. (2006). Metabolomics: Bringing nutrigenomics to practice in individualized health assessment. In Nutritional Genomics. Eds Jim Kaput & Raymond Rodriguez. John Wiley & Sons, New Jersey. Pg. 85-104.
  • Ward R.E., German J.B. and Corredig M. (2005) Composition, applications, fractionation, technological and nutritional significance of milk fat globule membrane material. In: Advanced Dairy Chemistry, Vol 2: Lipids, 3rd ed, Fox P.F. and McSweeney P. (eds), Springer, NY, pp. 213.
  • German JB, Schanbacher FL, Lonnerdal B, Medrano J, McGuire MA, McManaman JL. Rocke DM, Smith TP, Neville MC, Donnelly P, Lange MC, and Ward RE. (2006) International milk genomics consortium Trends Food Science & Technology Volume 17, Issue 12, 656-661.
  • Chardigny,Jean-Michel Corinne Malpuech-Brugere, Fabiola Dionisi, Dale E. Bauman, Bruce German, Ronald P. Mensink , Nicole Combe Patrice Chaumont, David M. Barbano, Francis Enjalbert Jean-Baptiste Bezelgues, Isabelle Cristiani, Julie Moulin Yves Boirie, Pierre-Alain Golay, Francesca Giuffrida, Jean-Louis Sebedio Frederic Destaillats (2006) Rationale and design of the TRANSFACT project phase I: A study to assess the effect of the two different dietary sources of trans fatty acids on cardiovascular risk factors in humans Contemp Clin Trials. 27(4):364-73.
  • Ninonuevo MR, Park Y, Yin H, Zhang J, Ward RE, Clowers BH, German JB, Freeman SL, Killeen K, Grimm R, Lebrilla CB. 2006 A strategy for annotating the human milk glycome. J Agric Food Chem;54(20):7471-80.
  • German J.B. and Dillard C.J. (2006) Composition, structure, and absorption of milk lipids: a source of energy, fat soluble nutrients and bioactive molecules. Critical Reviews in Food Science and Nutrition 46(1):1-36.


Progress 01/01/05 to 12/31/05

Outputs
Research has sought to understand how lipids alter the mechanistic machinery of animals. Using a strategy of feeding animals diets varying in only the amount of long chain polyunsaturated fatty acids we have been able to define the various consequences on the metabolism of these animals. These studies found that the inclusion of polyunsaturated fatty acids to the diets of these animals had both acute metabolic effects, i.e. altered the membrane composition of cells and tissues, but also influenced the expression of families of genes in these animals (Mutch et al. FASEB J). Some genes were expected, e.g. those responsible for adding double bonds to fatty acids, but the overall metabolic machinery of the animals was altered as well. The gene encoding the enzyme stearoyl CoA desaturase 1 was down-regulated in response to feeding arachidonic acid. This gene has been implicated in the development of obesity and predisposition to diabetes that is a consequence of obesity. These results imply that arachidonic acid in the diet acts to alter the basic energetic machinery in cells and could represent a novel strategy for understanding and ultimately preventing the energy disregulation that can lead to obesity. Studies have also examined the consequences of consuming milk. There are excellent scientific reasons to study milk since this is the only biomaterial that evolved for the express purpose of nourishing mammals. Therefore we have been interested in understanding how milk affects overall metabolism and in particular energy metabolism, a particular challenge to the young neonate. Milk has also proven to be not just a supplier of nutrients but is emerging as a model of how diet can be an important controller of overall metabolism, improving the storage of excess lipids as adipose and avoiding the inappropriate accumulation of energy intermediates in blood (Smilowitz et al. Aust. J. Dairy Tech.). Because metabolic disregulation is emerging as such a problem to human health we have continued to develop the technologies necessary to measuring metabolism in a comprehensive manner and especially with the accuracy and precision necessary to be able to detect the normally subtle consequences of consuming dietary fats and other macronutrients (Ninonueva et al., Electrophoresis, German et al., Metabolomics). We have also been requested to provide conceptual articles as the means to educate and recruit the larger nutrition community in the USA and around the world to the applications of this approach both for scientific research in Nutritional Sciences, but also to its ultimate applications as foods for human health (Zeisel et al., JN, Gibney et al. AJCN). It is also important to understand how the modern food consumer receives information about foods and diets, how the consumer interprets this information in terms of their own health and how these sources of information ultimately influence food choices. We have examined the internet as a very modern and potentially revolutionary information source for consumers about foods and diets, their risks and benefits (Moskowitz et al.CRFSN).

Impacts
The lipid components of food provide desirable organoleptic properties to consumers, challenges to agriculture in quality and safety and are implicated in the overall health consequences of foods and diets. To improve the overall quality of foods and diets, it is necessary to build an integrated view on the lipids to understand simultaneously their benefits and liabilities. Polyunsaturated fatty acids exhibit metabolic effects but also influence the expression of multiple genes in animals (Mutch et al. FASEB J). Milk is a model of how diet can be an controller of overall metabolism (Smilowitz et al. Aust. J. Dairy Tech.). We have developed technologies to measure the consequences of diet (Ninonueva et al., Electrophoresis, German et al., Metabolomics), and been invited to recruit the nutrition community to this approach (Zeisel et al., JN, Gibney et al. AJCN). It is important to know how the food consumer receives and interprets information about foods and diets in terms of their own health and how these sources of information ultimately influence food choices (Moskowitz et al.CRFSN). Altogether the research is illustrating that critical knowledge of dietary fats is still lacking and designing optimal foods and diets will require the means to both understand the metabolic differences between individuals and to understand the metabolic consequences of consuming different dietary fats. Professional scientists such as dieticians will need to acquire a greater knowledge of how to guide individual consumers to optimal diets (German et al., JADA).

Publications

  • Mutch D. David M. Mutch; Martin Grigorov; Alvin Berger; Laurent B Fay; Matthew Roberts, Steven M Watkins; Gary Williamson; J Bruce German An integrative metabolism approach identifies stearoyl-CoA desaturase as a target for an arachidonate-enriched diet. FASEB Journal 2005 electronic publication on line. German J.B. Hammock B.D. and Watkins S.M. Metabolomics: building on a century of biochemistry to guide human health Metabolomics 1, 1, 3-8 2005 German J.B. Genetic dietetics: Nutrigenomics and the future of dietetics practice J Am Diet Assoc. 2005 Apr;105(4):530-1. Pecquet S, Prioult G, Campbell J, German B, Turini M. Commonly used drugs impair oral tolerance in mice Ann N Y Acad Sci. 2004 Dec;1029:374-8 Smilowitz, J. L. Dillard C.J. and German J.B. Milk beyond essential nutrients: the metabolic food. Australian Journal of Dairy Technology volume 60 no 3 77-83 Moskowicz, H. German J.B. and Saguy S. Unveiling Health Attitudes and creating good-for-you Foods via Informatics & Innovative Web-Based Tec


Progress 01/01/04 to 12/31/04

Outputs
Research in the past year has developed further our understanding of the physical, chemical and biological properties of dietary lipids and their specific roles in foods and health. The nutritional value of the wide range of lipids from milk has continued to be a source of controversy as the potential beneficial and detrimental properties are explored. Research illustrates that different fatty acids are likely to have disparate effects on different individuals based on their genetic and metabolic status. Therefore strategies to distinguish metabolic differences between individuals were an important outcome of the project this year. Methods were developed to quantify the broad metabolic effects of various dietary ingredients including but not limited to dietary fats. Since individual metabolism responds to non-essential nutrients International consensus was developed to pursue the means to coordinate research in personalized assessment and dietary intervention. The continuing goals of this research are to provide the analytical tools to enable individuals to routinely monitor their metabolic health and with this information guide their food choices.

Impacts
Understanding the role of dietary lipids in health and metabolism will provide the knowledge for the food industry to produce food products for improved health. A scientific consensus to establish the metabolic differences between individuals and their different responses to diet will guide the development of technologies to measure those differences and inform both the consumers and their food providers.

Publications

  • GERMAN, J.B., YERETZIAN, C. and WATZKE, H.J. 2004. Personalizing Foods for Health and Preference. Food Technology. In Press.
  • WARD, R.E., GERMAN, J.B. 2004. Understanding Milk's Bioactive Components: A Goal for the Genomics Toolbox J Nutr. 134(4):962S-7S
  • VEGA-LOPEZ, S., KAUL, N., DEVARAJ, S., CAI, R.Y., GERMAN, B., JIALAL, I. 2004. Supplementation with omega3 polyunsaturated fatty acids and all-rac alpha-tocopherol alone and in combination failed to exert an anti-inflammatory effect in human volunteers. Metabolism. 53(2):236-40
  • GERMAN, J.B. DILLARD, C.J. 2004. Saturated fats: What dietary intake? American Journal of Clinical Nutrition. 80:550-560.
  • MUTCH, D., GRIGOROV, M; BERGER, A.; FAY, LB; ROBERTS, M, WATKINS, SM; WILLIAMSON, G; GERMAN, JB 2004. An integrative metabolism approach identifies stearoyl-CoA desaturase as a target for an arachidonate-enriched diet. FASEB Journal. In press.
  • GERMAN, J.B., BAUMAN, D.E., BURRIN, D.G., FAILLA, M.L., FREAKE, H.C., KING,J.C., KLEIN, S., MILNER, J.A., PELTO, G.H., RASMUSSEN, K.M., ZEISEl, S.H. 2004. Metabolomics in the opening decade of the 21st century: building the roads to individualized health. J Nutr. 134(10):2729-32


Progress 01/01/03 to 12/31/03

Outputs
Research in the past year has developed further our understanding of the physical, chemical and biological properties of dietary lipids and their specific roles in foods. The biological and nutritional value of membrane lipids from milk represent an attractive food ingredient, and methods were developed to characterize the effects of processing on their composition and properties. Milk fat globules can be fractionated by directing mammary biosynthesis, and post-harvest by various methods that take advantage of the physical and biological properties of different sizes of globules. The nutritional consequences of consuming specific fatty acids were studied for their influence on mammalian immunological responses. Conjugated linoleic acid was found to not stimulate the immune system of immune-depleted mice. Oils containing 5,11,14 eicosatrienoic acid inhibited the inflammatory cascade and nephrotoxicity in a transplant model. Methods were developed to quantify the broad metabolic effects of various dietary ingredients including but not limited to dietary fats. Finally, individual metabolism is particularly susceptible to non-essential nutrients, and as the world's population is in the midst of a major epidemic of metabolic diseases (atherosclerosis, obesity, type2 diabetes, osteoporosis) it is critical to understand how non-essential components of foods affect health. Perhaps even more importantly, the tools to measure metabolic health comprehensively do not yet exist. The goals of this research are to provide the analytical tools to enable individuals to routinely monitor their metabolic health and with this information guide their food choices.

Impacts
Understanding the role of dietary lipids in human metabolism will allow the food industry to reformulate food products for improved health. Understanding the differences between individuals in their responses to diet will only be actionable when technologies are in place to measure those differences and inform both the consumers and their food providers.

Publications

  • Astaire, J.C. et al. 2003. Concentration of polar MFGM lipids from buttermilk by microfiltration and supercritical fluid extraction. J Dairy Sci. 86(7):2297-2307.
  • German, J. et al. 2003. Personal metabolomics as a next generation nutritional assessment. J. Nutr. 133(12):4260-4266
  • German J.B., Dillard, C.J. and Ward, R.F. 2003. Milk: A model for nutrition in the 21st century. Australian Journal of Dairy Technology 58(2):72-77.
  • German, J.B. 2003. Implications of genomics for food and health. Australian Journal of Dairy Technology 58(2):38-44.
  • Turini, ME et al. 2003. Short-term dietary conjugated linoleic acid supplementation does not enhance the recovery of immunodepleted dexamethasone-treated rats. Eur. J. Nutr. 42(3):171-179
  • German, J.B. Roberts, M.A. and Watkins, S.M. 2003. Personal metabolomics as a next generation nutritional assessment. J. Nutr. 133:2003
  • Boyle-Roden, E, German, J.B. and Wood, B.J. 2003. The production of lipids alternately labelled with carbon-13. Biomol. Engr. 20(4-6):285-289
  • Butani, L, A. et al. 2003. Amelioration of tacrolimus-induced nephrotoxicity in rats using juniper oil. Transplantation. 76(2):306-311
  • Ward, R.E. and German, J.B. 2003. Zoonutrients and Health. Food Technology 56(3):30-36
  • German, J. et al. 2003. Genomics and metabolomics as markers for the interaction of diet and health: Lessons from lipids. J. Nutrition 133(6 Suppl 1):2078S-2083S


Progress 01/01/02 to 12/31/02

Outputs
The composition and structures of lipids are important factors determining their nutritional, biological and biomaterial functions in foods and diets. In the past period, research has demonstrated new techniques to examine the physical properties and stability of complex biological colloidal structures and foods. We have continued to develop the scientific support for the importance of understanding the mechanisms behind variation in human responses to different diets. The research has illustrated the need for and begun to assemble analytical platforms to quantify individual metabolism in order for agriculture to establish truly optimal diets for the consumers of the future.

Impacts
Lipids contribute important physical and organoleptic properties to foods and influence preference for their selection. This research has provided new tools to investigate these properties and the nutritional rationale to investigate the individual responses of consumers to dietary fats.

Publications

  • Weiller, B.H. et al. 2002. Analysis of lipoproteins by capillary electrophoresis in microfluidic devices. Anal. Chem.74:1702-1711.
  • Medina, I. et al. 2002. Effects of natural phenolics on the antioxidant activity of lactoferrin in liposomes and oil-in-water emulsions. J Agr. Food Chem. 50:2392-2399.
  • Frankel, E.N. et al. 2002. Oxidative stability of fish and algae oils containing long-chain PUFA in bulk and in oil-in-water emulsions. J. Agr. Food Chem. 50:2094-2099.
  • Donovan, J.L. et al. 2002. Urinary excretion of catechin metabolites by human subjects after red wine consumption. British J. Nutr. 87:31-37.
  • Watkins, S,M, and German, J.B. 2002. Metabolomics and biochemical profiling in drug discovery and development. Current Opinion in Mol. Ther. 4:224-228.
  • Watkins, S.M. et al. 2002. Lipid metabolome-wide effects of the peroxisome proliferator-activated receptor gamma agonist rosiglitazone. J. Lipid Res. 10:1194.
  • German, J.B. et al. 2002. Bioactives in milk. Current Opinion in Clin. Nutr. and Metabolic Care. In Press.
  • Berger, A. et al. 2002. Dietary effects of arachidonate-rich fungal oil and fish oil on murine hepatic and hippocampal gene expression. Lipids in Health and Disease 1:2.
  • Watkins, S.M. and German, J.B. 2002. Toward the implementation of metabolic assessment of human health and nutrition. Current Opinion in Biotech. 13:512-516.


Progress 01/01/01 to 12/31/01

Outputs
This project is helping to build the scientific knowledge necessary to optimize the composition of fats to produce more valuable and healthy foods. During the past year we have demonstrated the importance of lipids to the absorption of essential nutrients, and recommended that fat soluble vitamins be restored to fat-reduced foods. We have demonstrated the potential of complex lipids to modify the growth of cancer cells and argued for the expansion of this research field as a means to influence the incidence of gastrointestinal cancers in humans and animals. Finally, we have demonstrated the importance of lipid metabolism as a reflection of overall health and argued for the use of metabolomic techniques to accurately reflect the overall status of health of individual humans rather than to rely on simple biomarkers of disease risk. We have moved the laboratory research objectives to include genomic knowledge as an important resource of the future and published on its importance to nutrition in general.

Impacts
Lipids of foods provide positive aspects of food from structure to promoting growth and immunity, yet lipids produce negative aspects from food deterioration to promoting heart disease. Thus, the value of foods depends in part on optimizing the lipids. This research has provided means to stabilize lipids, to improve their nutritional impact and to demonstrate their nutritional value in diets.

Publications

  • Watkins, S.M., et al. 2001. Unique phospholipid metabolism in mouse heart in response to dietary docosahexaenoic or a-linolenic acids. Lipids 36: 247-254.
  • Quasney, M.E., et al. 2001. Inhibition of proliferation and induction of apoptosis in SNU-1 human gastric cancer cells by the plant sulfolipid, sulfoquinosyldiacylglycerol. J. Nutr. Biochem. 12:310-315.
  • Watkins, S.M., et al. 2001. Individual metabolism should guide agriculture toward foods for improved health and nutrition. Am. J. Clin. Nutr. 74:283-286.
  • Roberts, M.-A., et al. 2001. Genomics: food and nutrition. Current Opinion in Biotech. 12:516-522.
  • Schramm, D.D., et al. 2001. Chocolate procyanidins decrease the leukotriene-prostacyclin ratio in humans and human aortic endothelial cells. Am. J. Clinical Nutr. 73:36-40.
  • German, J.B. and Traber, M.G. 2001. Nutrients and oxidation: Actions, transport and metabolism of dietary antioxidants. In: HANDBOOK OF VITAMINS, V.3, Rucker, R.B., et al., eds, Marcel Dekker, Inc., New York, pp.569-588.
  • Watkins, S.M., et al. 2001. Lipids and immunity. In: ATHEROSCLEROSIS AND AUTOIMMUNITY, Shoenfeld, Y., et al., eds, Elsevier Sci., Amsterdam, pp.87-111.
  • DePeters, E.J., et al. 2001. Fatty acid and triglyceride composition of milk fat from lactating holstein cows in response to supplemental canola oil. J. Dairy Sci. 84:929-936.
  • Kaushik, S., et al. 2001. Removal of fat from cow's milk decreases the vitamin E contents of the resulting dairy products. Lipids 36:73-78.
  • German J.B. 2001. Antioxidants. In: FOOD ADDITIVES, 2nd Ed., Branen A.L., et al., eds, Marcel Dekker, Inc., New York.


Progress 01/01/00 to 12/31/00

Outputs
The lipid or fatty component is responsible for much of the beneficial sensory attributes of foods yet the over consumption of specific classes of fats is implicated in the etiology of many of the chronic diseases afflicting humans. Several health organizations have suggested that modulating the fatty acid composition of human diets would significantly improve the susceptibility to diseases such as heart disease, cancer and auto-immune diseases. Unfortunately an understanding of the mechanisms by which these beneficial effects might be acting and even the physical means to implement these changes on the typical western diet are largely unknown. This research project is developing the information that will allow more precise estimates of benefits (and risks) of modulating the lipid composition of foods. During the past year we have demonstrated that flavonoids from apples protect human LDL from oxidation ex vivo, and that flavonoids from olives protect polyunsaturated fatty acids of fish in foods. We have further demonstrated that the major flavonoid of red wine, catechin circulates primarily as conjugated metabolites in the plasma of humans. We have finally shown the growing conditions that influence lipid composition of photoheterotrophic algae.

Impacts
Since plant flavonoids protect unsaturated lipids in foods and in blood, processes to increase specific flavonoids in foods would improve the risk of chronic diseases. True risk prediction will be possible by applying analytical chemistry to nutritional assessment by directly measuring individual human metabolic profiles rather than population estimates or individual food intake questionnaires.

Publications

  • Pearson D.A., Tan C.H., German J.B., Davis P.A. and Gershwin M.E. 1999. Apple juice inhibits human low density lipoprotein oxidation. Life Sciences 64(21):1913-1920.
  • Wood B.J.B, Grimson P.H.K, German J.B. and Turner M. 1999. Photoheterotrophy in the production of phytoplankton organisms. J. Biotech. 70(1-3):175-183.
  • Medina I., et al. 1999. Comparison of natural polyphenol antioxidants from extra virgin olive oil with synthetic antioxidants in tuna lipids during thermal oxidation. J. Agr. Food Chem. 47(12):4873-4879.
  • Bell J.R.C., Donovan J.L., Wong R., Waterhouse A.L., German J.B., Walzem R.L. and Kasim-Karakas S.E. 2000. (+)-Catechin in human plasma after ingestion of a single serving of reconstituted red wine. Am. J. Clinical Nutr. 71(1):103-108.
  • Roberts M., Geiger W. and German B. 2000. The revolution in microanalytic chemistry: a macro-opportunity for clinical nutrition. Am. J. Clinical Nutr. 71(2):434-437.


Progress 01/01/99 to 12/31/99

Outputs
The lipid or fatty component is responsible for much of the beneficial sensory attributes of foods yet the over consumption of specific classes of fats is implicated in the etiology of many of the chronic diseases afflicting humans. Several health organizations have suggested that modulating the fatty acid composition of human diets would significantly improve the susceptibility to diseases such as heart disease, cancer and auto-immune diseases. Unfortunately an understanding of the mechanisms by which these beneficial effects might be acting and even the physical means to implement these changes on the typical western diet are largely unknown. This research project is developing the information that will allow more precise estimates of benefits (and risks) of modulating the lipid composition of foods. During the past period we have demonstrated that the short chain fatty acid up-regulates the enzymes that produce Prostaglandin E2 and increases immunologic tolerance, and also induces cell death in cancerous cells by the process known as apoptosis. We have demonstrated that the polyunsaturated fatty acid docosahexaenoic acid when, accumulated in the inner mitochondrial lipid cardiolipin, stimulates oxidant production. Finally we have shown that flavonoids from plants alter the oxidation rate of lipids, and are well absorbed, taken up by cells and metabolized into conjugates that circulate in human blood.

Impacts
Butyric acid is produced by fermentation of fiber in the colon and is present in bovine milk fat. Results support that butyrate is of benefit for cancer prevention and for specific immunologic situations in which immune tolerance is desired. Plant flavonoids are desirable components and agricultural processes that increase net dietary flavonoid intake are recommended by this research.

Publications

  • Schramm, D.D. et al. 1999. Flavonoid transport by mammalian endothelial cells. J. Nutr. Biochem. 10:193-197
  • Pearson, D.A. et al. 1999. Apple juice inhibits human low density lipoprotein oxidation. Life Sciences 64:1913-1920.
  • Huang S.-W. et al. 1999. Effect of lactoferrin on oxidative stability of corn oil emulsions and liposomes. J. Agr. Food Chem. 47: 1356-1361.
  • Donovan, J.L. et al. 1999. Catechin is present as metabolites in human plasma after consumption of red wine. J. Nutr. 129: 1662-1668.
  • Watkins, S. et al. 1999. Butyric acid and tributyrin induce apoptosis in human hepatic tumor cells. J. Dairy Res. 66: 559-567
  • Perez, R.V. et al. 1998. Selective targeting of Kupffer cells with liposomal butyrate augments portal venous transfusion-induced immunosuppression. Transplantation 65:1294-1298
  • Perez, R. et al. 1998. Sodium butyrate up regulates Kupffer cell PGE2 production and modulates immune function. J. Surgical Res. 78:1-6


Progress 01/01/98 to 12/31/98

Outputs
PHYSICAL AND CHEMICAL PROPERTIES OF FOOD AND BACTERIAL LIPIDS: The composition of proteins and lipids making up a liposomal suspension has an important effect on the stability of the suspension to oxidation and antioxidants need to be selected that match to the interfacial properties of particular suspensions. Listeria monocytogenes, the food borne pathogen, respond rapidly to cold shock modifying the fatty acid and phospholipid compositions of cellular lipids. ROLE OF DIETARY FATS: The polyunsaturated fatty acid docosahexaenoic acid, when incorporated into the mitochondrial lipid cardiolipin, causes a substantial alteration in the oxidant production by the mitochondria within living cells. The short chain fatty acid butyric acid produces an increase in prostaglandin E2 production in hepatic Kupffer cells when delivered as liposomal suspensions, verifying a therapeutic strategy for improving success for immune function and transplanted organ tolerance. OXIDATION AND ANTIOXIDANT ACTIONS: Fruit-derived flavonoids have differential effects on the lipid membrane signaling of isolated cells depending on the extent of polyphenolic polymerization. Enhancing polymerization during fruit processing would have the net effect of reducing the effectiveness of these compounds in modifying the cellular activities after ingestion.

Impacts
(N/A)

Publications

  • King, A.J. et al. 1998. Rapid method for quantification of cholesterol in turkey meat and products. J. Food Sci. 63:382-385.
  • Mastronicolis, S.K. et al. 1998. Evidence of cold shock on the fatty acid composition of different lipid classes of the food-borne pathogen LISTERIA MONOCYTOGENES. Food Micro. 15:299-306.
  • Watkins, S.M. et al. 1998. Docosahexaenoic acid accumulates in cardiolipin and enhances HT-29 cell oxidant production. J. Lipid Res.
  • Perez, R. et al. 1998. Sodium butyrate up regulates Kupffer cell PGE2-production and modulates immune function. J. Surgical Res.
  • Perez, R. et al. 1998. Kupffer cell-mediated lymphocyte apoptosis: a PGE2-dependent mechanism of portal venous transfusion-induced immunosuppression? J. Surgical Res. 78:37-41.
  • Perez, R.V. et al. 1998. Selective targeting of Kupffer cells with liposomal butyrate augments portal venous transfusion-induced immunosuppression. Transplantation 65:1294-1298.
  • Schramm, D.D. et al. 1998. Differential effects of small and large molecular weight wine phytochemicals on endothelial cell eicosanoid release. J. Agr. Food Chem. 46(5):1900-1905.


Progress 01/01/97 to 12/01/97

Outputs
PHYSICAL PROPERTIES OF FOOD LIPIDS: Permeability and polymerization mechanization mechanical properties and interfacial interactions of whey protein isolate (WPI) as edible films and stabilized emulsions were studied. Cationic lipids were successfully used to transfect avian hepatoma LMH-2A cells. ROLE OF DIETARY FATS: The modulation of Kupfer cell arachidonic acid metabolism by portal venous transfusion is proposed as a mechanism of enhancing immunosuppression in organ transplantation. Clinical effects of nutritional modifications to T-cell function in immunity was reviewed. Neutral and polar lipids in LISTERIA MONOCYTOGENES were isolated and identified. OXIDATION AND ANTIOXIDANT MECHANISMS: Several reviews of the role of plant and wine phenolics on health and disease were published. Phytochemicals as antioxidants in oxidizing lipid systems were studied, including: antioxidant partitioning in oil-water systems; inhibition of endothelial cell-mediated LDL oxidation by plant phenols; and stimulation of endothelial cell PGI2 release by wine.

Impacts
(N/A)

Publications

  • PEREZ, R.V. ET AL. 1997. Portal venous transfusion up-regulates Kupffer cell cyclooxygenase activity: A mechanism of immunosuppression in organ transplantation. Transplantation
  • GERMAN, J.B. ET AL. 1997. Wine phenolics and targets of chronic disease. In: WINE: NUTRITIONAL AND THERAPEUTIC BENEFITS, ACS Series 661, Wash, DC, pp. 196-214.
  • PEARSON, D.A. ET AL. 1997. Inhibition of endothelial cell-mediated oxidation of low-density lipoprotein by rosemary and plant phenolics. J Agr Food Chem 45:578-582.
  • SCHRAMM, D.D. ET AL. 1997. Endothelial cell basal PGI2 release is stimulated by wine IN VITRO: One mechanism that may mediate the vascoprotective effects of wine. J Nutr Biochem 8:000-000.
  • GERMAN, J.B. 1997. Nutritional studies of flavonoids in wine. In: FLAVONOIDS IN HEALTH AND DISEASE, Marcel Dekker, NY, pp. 343-358.
  • MONAHAN, F.J. ET AL. 1997. Disulfide mediated polymerization of whey proteins in whey protein isolate-stabilized emulsions. Adv Exp Med
  • FAIRLEY ET AL. 1997. Interfacial interactions in edible emulsion films from whey protein isolate. Food Hydrocoll 11:245-252.
  • MASTRONICOLIS, S. ET AL. 1996. Isolation and fatty acid analysis of neutral and polar lipids of the food bacterium LISTERIA MONOCYTOGENES. Food Chem 57:451-456.
  • YOSHIDA, S.H. ET AL. 1996. Nutritional modification of T lymphocyte subsets: clinical implications and applications. Sem Clin Immunol
  • REIN, D. 1997. 1996. Nutrient actions of plant antioxidants. Ph.D. Dissertation, Univ Calif, Davis. 138 pp.


Progress 01/01/96 to 12/30/96

Outputs
PHYSICAL PROPERTIES OF FOOD LIPIDS: Saturated & monounsaturated monoacylglycerols altered the lipid composition & molecular mobility of lipoprotein surfaces in distinct ways. Effects of pH & temperature on protein unfolding & thiol/disulfide interchange reactions during heat-induced gelation of WPI were described, as was disulfide-mediated polymerization reactions & the physical properties of heated WPI-stabilized emulsions. ROLE OF DIETARY FATS: The first symposium on myriad biological effects of dietary arachidonic acid (AA) was assembled. 5,11,14-Eicosatrienoic acid, a fatty acid that replaces AA in tissues, decreased pentobarbital-related mortality in an animal inflammation model. AA & docosahexaenoate were higher in liver but lower in adipose of growth hormone transgenic mice. The diverse nature of polar lipids in LISTERIA MONOCYTOGENES was shown. OXIDATION AND ANTIOXIDANT MECHANISMS: Phytochemicals as antioxidants in different oxidizing lipid systems were studied. The antioxidant activity of carnosol & carnosic acid from rosemary indicated their conversion to compounds with high activity. Comparison of alpha-tocopherol & Trolox activities in bulk oils vs oil-in-water emulsions showed that linoleic acid may not be a valid substrate for evaluating food antioxidants. A new method to determine lipid hydroperoxides was developed, & multiple aldehyde-peroxidation products were measured by GC/stable isotope dilution mass spectrometry.

Impacts
(N/A)

Publications

  • BOYLE, E. ET AL. 1996. Monoacylglycerols alter the lipid comp. and molecular nmobility of phosphatidylcholine bilayers... J Lipid Res 37:764-772.
  • BRUENNER, B.A. ET AL. 1996. Simultaneous determination of multiple aldehydes in biological tissues and fluids using gas chrom/stable isotope dilution mass spec.Anal Biochem 241:212-219.
  • GERMAN, J.B. ET AL. 1996. The biological effects of dietary arachidonic acid. J Nutr 126:S1076-S1080.
  • GERMAN, J.B. ET AL. 1996. Effect of dietary fats and barley fiber on total cholesterol and lipoprotein cholesterol distribution in plasma of hamsters. NutrRes 16:1239-1249.
  • HOPIA, A.I. ET AL. 1996. Effect of different lipid systems on antioxidant activity of rosemary constituents carnosol and carnosic acid with and w/out a-tocopherol. J Agr Food Chem 44:2030-2036.
  • HUANG, S.W. 1996. Interfacial lipid oxidation: Antioxidant activity in differentlipid systems. PhD Dissertation, Univ California, Davis. 150 pp.
  • MASTRONICOLIS, S. ET AL. 1996. Diversity of the polar lipids of the food-borne pathogen LISTERIA MONOCYTOGENES. Lipids 31:635-640.
  • MONAHAN, F.J. ET AL. 1996. Disulfide-mediated polymerization reactions and physical properties of heated WPI-stabilized emulsions. J Food Sci 61:504-509.
  • SCHWARZ, K. ET AL. 1996. Partition behavior of antioxidative phenolic compounds.


Progress 01/01/95 to 12/30/95

Outputs
Progress is reported on phys. chem. of lipids in foods, the role of diet. fats on tissue funct. & mechanisms of oxidation & antioxidants. Butterfat & tripalmitin blends can be used as moisture barriers in edible films. Continuing studies demo'd that such barrier properties depend more on morp. than polymorphic form. In vitro studies showed enhancement of oxidative stability in bulk oils by mixtures of tocopherols is determined by inhib. of hydroperoxide formation rather than of hydroperoxide decomposition. Evidence for mol. & genetic effects of diet. butyric acid, which constitutes up to 10 percent of milk fatty acids, was reviewed. In the form of tributyrin, butyric acid was shown to enhance the expression of a reporter gene in cell lines. Based upon our res. on oxidation of LDL particles, we dev'd math. models suggesting a linking mech. for the lipid & oxidation theories of atherosclerotic card. disease. Overwhelming evidence for influence of diet. micronut. antioxidant compounds on cancer & anticarcinogenesis was presented (intl. nutr./cancer symp). Continuing in vivo studies on diet. oleic anilide showed decreased 12-hydroxyeicosatetraenoic acid prod. in mouse lungs. This finding is relevant to immunoregulation & autoimmune syndromes in Toxic Oil Syndrome patients. Electrospray mass spec was used to characterize protein adducts formed by exposure of model proteins to 4-hydroxy-2-nonenal. Clearly, >99 percent of the adducts were formed by Michael addn, not as Schiff bases.

Impacts
(N/A)

Publications

  • FAIRLEY, P. ET AL. 1995. Crystal morphology of mixtures of tripalmitin & butterfat. JAOCS 72:693.
  • BRUENNER, B. ET AL. 1995. Direct char. of protein adducts of the lipid peroxidation product 4-hydroxy-2-nonenal using elec. mass spec. Chem Res Tox 8:552.
  • HUANG, S. ET AL. 1995. Effects of indiv. tocopherols & tocopherol mix. on the oxidative stab. of corn oil triglycerides. Agr Fd Chem 43:2345.
  • YOSHIDA, S. ET AL. 1995. Decrease of 12-hydroxyeicosatetraenoic acid prod. in mouse lungs following diet. oleic anilide consumption. Arch Env Contam Tox 28:524.
  • SMITH, J. ET AL. 1995. Incorporation of tributyrin enhances the expression of a reporter gene in primary & immortalized cell lines. Biotech 18:852.
  • SMITH, J. & GERMAN, J. 1995. Molecular & genetic effects of dietary derived butyric acid. Fd Tech 49:87.
  • WALZEM, R. ET AL. 1995. Older plasma lipoproteins are more susceptible to oxidation. Proc Natl Acad Sci 92:7460.


Progress 01/01/94 to 12/30/94

Outputs
Progress is reported concerning the physical chemistry of lipids in foods, and the role of dietary fats on tissue function and on lipid oxidation. Triglycerides from milkfat were isolated and separated. The tendency to promote crystallization and plasticity in milkfat assigned to the fully saturated species, which contain a saturated fatty acid on all three positions on the glycerol. Since the products of lipoprotein hydrolysis would be saturated monoglycerides, which we have also shown alter surface structure and subsequent metabolism, this is an important property of milkfat. We continue to define the specificity of fatty acid incorporation into tissues. We demonstrated that the unusual non-methylene interrupted fatty acids are readily incorporated into certain tissue membranes replacing arachidonic acid. This replacement in an animal model of autoimmunity, the NZB mouse prolonged its survival, suggesting that this fatty acid would have therapeutic value in certain human diseases. In ongoing studies on the composition and oxidative stability of circulating lipoproteins in humans we have demonstrated that phenolics inhibit the oxidation of lipid emulsions, vesicles and lipoproteins, and may thus have significant nutritional value as biological protectants.

Impacts
(N/A)

Publications

  • KANNER, K., FRANKEL, E., GRANIT, R., GERMAN, B. and KINSELLA, J.E. 1994. Natural antioxidants in grapes and wines. J. Agr. Food Chem. 42(1):64-69.
  • FRANKEL, E.N., PARKS, E.J., XU, R., SCHNEEMAN, B.O., DAVIS, P.A. and GERMAN, J.B. 1994. Effect of n-3 fatty acid-rich-fish oil supplementation on oxidation of low density lipoproteins. Lipids 29(4):233-236.
  • PILHOFER, G., LEE, A., MCCARTHY, M.J., TONG, P.S. and GERMAN, J.B. 1994. Functionality of milkfat in foam formation and stability. J. Dairy Sci. 77(1):55-63.
  • YOSHIDA, S.H., GERMAN, J.B., FLETCHER, M.P. and GERSHWIN, M.E. 1994. The toxic oil syndrome: A perspective on immunotoxicological mechanisms. Reg. Tox. Pharm. 19(1):60-79.
  • LAI, L.T., NAIKI, M., YOSHIDA, S.H., GERMAN, J.B. and GERSHWIN, M.E. 1994. Dietary PLATYCLADUS ORIENTALIS seed oil suppresses anti-erythrocyte autoantibodies and prolongs survival of NZB mice. Clin. Immun. Immunopath. 71(3):293-302.
  • FAIRLEY, P., GERMAN, J.B. and KROCHTA, J.M. 1994. Phase behavior and mechanical properties of tripalmitin/butterfat mixtures. J. Food Sci. 59(2):321-325.
  • FRANKEL, E.N., HUANG, S.W., KANNER, J. and GERMAN, J.B. 1994. Interfacial phenomena in the evaluation of antioxidants: Bulk oils versus emulsions. J. Agr. Food Chem. 42(5)1054-1059.


Progress 01/01/93 to 12/30/93

Outputs
Progress is reported for the physical chemistry of lipids in foods, the role of dietary fats on tissue function and on lipid oxidation. The composition of triglycerides affects the rate and extent of fat crystallization in food emulsions. We have found that we can direct the crystallization rate by modifying the properties of the surface using surfactants. We have similarly demonstrated that monoglycerides alter the catalytic rates of surface active enzymes. Thus, the products of lipoprotein hydrolysis are important determinants in regulating lipoprotein and membrane remodeling. Furthermore, since diet modifies the lipid structures, this represents a key factor in dietary modification of lipoprotein clearance. We continue to define the specificity of fatty acid incorporation into tissues. We demonstrated that uptake of fatty acids into brain was much more precise and clearly regulated by different mechanisms than into other tissues. Thus, unusual non-methylene interrupted fatty acids are very poorly incorporated into membranes of brain. In ongoing studies on the composition and oxidative stability of circulating lipoproteins in humans we have found that the cholesterol ester core of these particles oxidizes most rapidly and that the phenolics in wine and other fruits are excellent antioxidants in vitro. We further proposed that this activity could partially explain the paradoxically low incidence of coronary disease in populations consuming red wine.

Impacts
(N/A)

Publications

  • SIMONEAU, C., MCCARTHY, M., REID, D. and GERMAN, J.B. 1993. Influence of triglyceride composition on crystallization kinetics of model emulsions. J. Food Engr. 19:365-387.
  • BOYLE, E. and GERMAN, J.B. 1993. Effect of physical properties and molecular composition on membrane interactions: a study of colloidal lipid particles. In: RECENT ADVANCES IN FOOD SCIENCE AND NUTRITION, Proceedings, 7th International Conf.
  • LAI, L.T.Y. and GERMAN, J.B. 1993. Modification of fatty acid composition in murine brain by dietary unsaturated fats. J. Nutr. Biochem. 4:463-472.
  • FRANKEL, E., KANNER, J. GERMAN, J.B. PARKS, E. and KINSELLA, J.E. 1993. Inhibition of oxidation of human low-density lipoprotein by phenolic substances in red wine. Lancet 341: 454-457.
  • XU, R., HUNG, S.O. and GERMAN, J.B. 1993. Utilization of different dietary lipids by white sturgeon. J. Nutr. 123:1685-1692.
  • BERGER, A. GERSHWIN, M.E. and GERMAN, J.B. 1993. Cardiolipin, biochemistry and nutrition. Advances in Food and Nutr. Res. 37:260-338.
  • SIMONEAU, C. MCCARTHY, M.J. and GERMAN, J.B. 1993. Magnetic resonance imaging and spectroscopy for food systems. Food Res. Intl. 26:387-398.


Progress 01/01/92 to 12/30/92

Outputs
Progress is reported for our three perspectives in research; the physical chemistry of fats in foods, the role of dietary fatty acids on tissue composition and function and the role of lipoxygenases in lipid oxidation. We have found that monoglycerides modify the crystallization behavior of pure triglycerides and triglyceride mixtures in foods using NMR imaging and verified these results using Differential Scanning Calorimetry. These approaches are continuing to define the targets to modifying fat functions in foods. We have shown that there is considerable specificity in different tissues for the uptake of fatty acids from the diet. In particular, one advance is important for our continued work. We have extended our previous work on the regulation of desaturation and elongation to show that polyunsaturated fatty acids which are products of the desaturation and elongation enzymes accumulate to a greater extent in membranes relative to their precursors. This implies that diets which are rich in these fatty acids will significantly alter membrane composition. We have also identified the unique competitiveness of non-methylene interrupted fatty acids, a distinct class of unsaturated fatty acids, for incorporation into membranes. In ongoing research on the lipoxygenase of fish tissue we have found that substrate liberation by cellular phospholipases determines the net metabolism by the enzymes in fish.

Impacts
(N/A)

Publications

  • PILHOFER, G., KAUTEN, R., MCCARTHY, M.J. and GERMAN, J.B. 1991. Phase separation in optically opaque emulsions. J. Food Engineering. in-press.
  • BERGER, A., GERSHWIN, M.E. and GERMAN, J.B. 1992. Effects of various dietary fats on cardiolipin acyl composition during ontogeny of mice. Lipids 27:605-612.
  • BERGER, A., GERMAN, J.B. and GERSHWIN, M.E. 1992. Implications of modifying cardiolipin acyl composition by diet 1. cardiolipin acyl chain is an important determinant in the binding to antiphospholipid antibodies in SLE Sera. J.
  • GERMAN, J.B., BERGER, R. and ZHIANG, H.J. 1992. The role of lipoxygenases in lipid oxidation of fish. In: LIPID OXIDATION IN FOOD. ST. ANGELO, A., ed., ACS Symposium Series, ACS, Washington, D.C. 500:74-93.
  • FRANKEL, E.N., GERMAN, J.B. and DAVIS, P. 1992. Headspace gas chromatography to determine human LDL oxidation. Lipids 27:1047-1051.
  • SIMONEAU, C., MCCARTHY, M.J., REID, D.S. and GERMAN, J.B. 1992. Measurement of fat crystallization using NMR imaging and spectroscopy. Trends in Food Sci. & Tech. September 1992:208-211.
  • OZILGEN, S., SIMONEAU, C., GERMAN, J.B., MCCARTHY, M.J. and REID, D.S. 1992. Crystallization kinetics of emulsified triglycerides. J. Sci. Food Agr. In Press.


Progress 02/01/88 to 12/30/91

Outputs
Progress is reported for our three perspectives in research; the physical chemistry of fats in foods, the role of dietary fatty acids on tissue composition and function and the role of lipoxygenases in lipid oxidation. We have demonstrated the crystallization behavior of pure triglycerides and triglyceride mixtures in actual food models using NMR Imaging and verified these results using Differential Scanning Calorimetry. These approaches are continuing to define the targets to modifying fats in foods. We have shown that there is considerable specificity in different tissues for the uptake of fatty acids from the diet. In particular one advance is important for our continued work. We were very interested in the difference between short and long chain n-3 fatty acids in delivering long chain fatty acids to tissues. To put it in commercial terms is linseed comparable to fish oil? With respect to many aspects the two were similar but we have demonstrated that the long chain highly oxidizable fatty acid 22:6 accumulates in the mitochondrial phospholipid cardiolipin to a far greater extent if fed intact as compared to fed as its metabolic precursor 18:3 n3. We have extended this with other studies to show that the peroxisome is an important regulator of fatty acid composition. In ongoing research on the lipoxygenases of fish tissue we confirmed that this enzyme class is responsible for much of the 'fresh' flavor associated with fresh fish.

Impacts
(N/A)

Publications

  • BERGER, A. and GERMAN, J.B. 1989. Incorporation of a linolenate (18:3n-3) and eicosatrienoate (20:3n-3) into the phospholipids of various mouse tissues. Lipids 25(8):473-480.
  • GERMAN, J.B. 1990. Properties of stabilizing components in foams. In: AIChE SYMPOSIUM SERIES FOOD EMULSIONS AND FOAMS: THEORY AND PRACTICE, WAN, P., ed., 86:62-71.
  • GERMAN, J.B., BERGER, R.G. and DRAWERT, F. 1991. Generation of fresh fish volatiles: rainbow trout (SALMO GAIRDNERI) gill homogenates as a model system. Food Chemistry Microbiology Technology 13:19-24.
  • SIMONEAU, C., MCCARTHY, M.J. and GERMAN, J.B. 1991. Crystallization dynamics in emulsions using nuclear magnetic resonance imaging. J. Am. Oil Chem. Soc. 68(7):481-487.
  • KEEN, C., GERMAN, J.B., MARESCHI, J. and GERSHWIN, M.E. 1991. Nutritional modulation of murine models of autoimmunity. In: NUTRITION AND RHEUMATIC DISEASES, PANUSH, R.S., ed., Saundes CO., Philadelphia, PA, 17(2):223-234.
  • BERGER, A. and GERMAN, J.B. 1991. Extensive incorporation of 5,11,14 eicosatrienoic acid into the phosphatidyl inositol class of membrane lipids. Biochim. Biophys. Acts 1085(3):371-376.


Progress 01/01/90 to 12/30/90

Outputs
This summary reports progress in our research to understand the functional role of fats and the effects which specific fatty acids in the diet exert on biological processes as a goal to optimize the health value of the fat component of foods. Using nutritional experiments we determined that omega or n-3 polyunsaturated (PUFA) fatty acids from plants (linseed oil 18:3 n3) and fish (20:5 n3 + 22:6 n3) are metabolized differently. Whereas both sources of n-3 PUFA modify arachidonic acid (20:4 n6) levels in tissues consistent with a desirable shift in eicosanoid precursors, preformed 22:6 n3 is selectively accumulated in the mitochondrial phospholipid cardiolipin but not if ingested as its precursor 18:3 n3. Thus the precise form of dietary n-3 polyunsaturated fatty acid is important. We are pursuing consequences of 22:6 in cardiolipin. The lipoxygenases we found in fish are responsible for volatile products released3ed by fresh fish tissues. Flavor in such foods is hence related to the reactions of endogenous oxidative enzymes which lose their activity during processing and storage. We are continuing to improve our understanding of how to regulate these enzymes.Using our relaxation weighted magnetic resonance imaging techniques to quantify the fat in foods we have followed the crystallization of purified triglycerides. we have shown that crystallization kinetics are dependent on the species of triglyceride, the states of dispersion, the presence of nucleii and the temperature.

Impacts
(N/A)

Publications

  • GERMAN, J.B. and CREVELING, R.C. 1989. Identification and characterization of a 15 lipoxygenase in fish gill. J. Ag. and Food Chem. 38:2144-2147.
  • GERMAN, J.B. and PHILLIPS, L.G. 1989. Molecular properties of proteins important in foams. In: FOOD PROTEINS, KINSELLA, J.E. and SOUCIE, W.G., eds., American Oil Chemists' Society, Champaign, IL, pp. 132-143.
  • GERMAN, J.B. and BERGER, R. 1990. Formation of 8,15 diHETE by sequential reaction with the 15 and 12 lipoxygenase in fish gills. Lipids 25(12):849-854.
  • PHILLIPS, L.G., GERMAN, J.B., O'NEILL, T.E., FOEGEDING, E.A., HARWALKAR, V.R., KILARA, A., LEWIS, B.A., MANGINO, M.E., MORR, C.V., REGENSTEIN, J.M., SMITH, D.M. and KINSELLA, J.E. 1990. Standardized procedure for measuring foaming prop.
  • HEIL, J.R., MCCARTHY, K.L., GERMAN, J.B., MCCARTHY, M.J. and PATINO, H. 1990. Use of magnetic resonance imaging for evaluation of beer foam characteristics. J. Am. Soc. Brew. Chem. 48:119-122.
  • WINKLER, M., MCCARTHY, M.J. and GERMAN, J.B. 1991. Noninvasive quantitation of lipids in foods using MRI. J. Food Sci. 56:811-815.


Progress 01/01/89 to 12/30/89

Outputs
Progress is reported in our research in the effects of specific fatty acids in the diet on physiolocal functioning of cells and tissues, the role of endogenous enzymes on lipid deterioration in foods and tissues and the role of fat in the structure and textural properties of multiphase foods such as foams and emulsions. Work is based on the underlying assumption that only by understanding both the functional role of fats in foods and the specific effects which fatty acids in the diet exert on biological processes can we ultimately optimize nutritional quality of this component. Dietary experiments were designed to answer questions about the regulation using fatty acids not normally found in diets. We found convincing evidence that these unique fatty acids are readily retroconverted to essential fatty acids only in certain organs but are then available to all tissues. This opened a means to investigate the regulation of absolute levels of all the essential fatty acids and their physiological function. We showed that similar lipoxygenses in both fish gills and animal lungs are sensitive to oxidative stress either through external prooxidants or through inhibition of glutathione peroxidase by pharmacological agents such as gold. We also found that two separate lipoxygenases in fish tissues act sequentially to produce multiply oxygenated polyunsaturated fatty acids.

Impacts
(N/A)

Publications

  • BERGER, R., MACKU, C., GERMAN, J.B. and SHIBAMOTO, T. 1989 Identification and characterization of dry salami volatiles, J. Food Sci. (in-press.).
  • MCCARTHY, K.L., MCCARTHY, M.J. and GERMAN, J.B. 1989. Modeling of foam drainage and collapse: incorporation of vertical mass distribution. Proceedings of the 5th International Congress on Engineering and Food, Cologne, Fed. Rep.-Germany.
  • MCCARTHY, M.J., MCCARTHY, K.L., GERMAN, J.B. and WINKLER, M. 1989. Foam and emulsion stability: measurements by magnetic resonance imaging. Proceedings of the 5th Internation Congress on engineering and Food, Cologn, Fed. Rep. of Germany.
  • MCCARTHY, M.J., CHAROENREIN, S., GERMAN, J.B., MCCARTHY, K.L. and REID, D.S. 1989. Phase volume measurements using magnetic resonance imaging. American Chemical Society, (in-press.).
  • GERMAN, J.B. and HU, M. 1989. Oxidant stress inhibits the endogenous production of lipoxygenase metabolites in rat lung and fish gills. J. Free Radicals in Biology and Medicine. (in-press.).
  • BERGER, A. and GERMAN, J.B. 1989. Incorporation of a linolenate (18:3n-3) and eicosatrienoate (20:3n-3) into the phospholipids of various mouse tissues. Lipids. (Accepted).
  • WINKERL, M.M. 1989. Quantification of fat and water in food systems using MRI.


Progress 01/01/88 to 12/30/88

Outputs
The preliminary results of nutritional studies indicate considerable selectivityin in corporation of dietary fats differing in chain length and unsaturation into some phospholipids but not in others. In the past year we have identified the 12 lipoxygenase enzyme in marine fishes and the stereochemistry as (S) and the hydrogen abstraction site as C n-11 of this reaction on polyunsaturated fatty acids. We have characterized the major products formed from endogenous fatty acids by this enzyme and have found that the gills of fish and the lungs of mammals make essentially the same products on tissue disruption: 12(S) HETE. Modeling studies suggested that high levels of hydroperoxides would inactivate the enzyme in vivo. This prediction was tested in actual experiments using exogenous hydroperoxides and found to be true in both fish gills and mammalian lungs. Mangnetic resonance imaging (MRI) and coupled kinetic modeling of unstable food systems has been developed and we have submitted a publication on the utility of this method in dynamic analyses, In preliminary experiments we have developed model systems in which the fat and aqueous phases are chemically well characterized and have provided data that these two phases can be simultaneously but separately imaged using MRI. We have also shown that ice cream, a classic model of structural stability attributable to its fat component, can be investigated using this new technique.

Impacts
(N/A)

Publications

  • GERMAN, J.B. and PHILLIPS, L. (1988). Properties of protein structure important for foams. J. Am. Oil Chem. Soc. (in-press).
  • GERMAN, J.B. and MCCARTHY, M. (1988). Stability of aqueous foams; analysis using magnetic resonance imaging. (submitted, J. Ag. Food Chem).