Source: PURDUE UNIVERSITY submitted to NRP
DEVELOPMENTAL PROGRAMMING OF ADIPOSE TISSUE DEVELOPMENT
Sponsoring Institution
National Institute of Food and Agriculture
Project Status
COMPLETE
Funding Source
HATCH
Reporting Frequency
Annual
Accession No.
0214933
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
PURDUE UNIVERSITY
(N/A)
WEST LAFAYETTE,IN 47907
Performing Department
Animal Sciences
Non Technical Summary
Obesity affects millions of young Americans of all races, increasing the risks of metabolic diseases such as diabetes and cardiovascular problems. In the US, a striking 17% of youths ages 2 to 19 years are considered obese or at risk of becoming obese. Predisposition to obesity is associated with an adverse in utero environment during fetal development that may be alleviated or exacerbated during postnatal life. Nutritional inadequacy during fetal development and during early postnatal period is the most significant predisposing factor for postnatal obesity. Epigenetic modifications to critical genes that regulate appetite, metabolism and tissue development determine the pattern of postnatal development and manifestation of disease. Critical gaps still exist in our knowledge of the specific genes that mediate the effect of inadequate nutrition during fetal and early postnatal life. Our long term goal is to determine the targets of identified histone modifying enzymes and their role during adipogenesis. This research will lead to a better understanding of the biological underpinnings of prenatal and postnatal nutrition on obesity susceptibility and excessive adipose tissue development. This is critical in developing specific mitigating strategies for obesity prevention. Poor fetal nutrition, resulting from inadequate maternal nutrition and poor neonatal nutrition are key events that preprogram off spring to excessive adipose tissue formation. For example inadequate protein and calorie consumption during pregnancy leads to offspring that are small for gestational age and who are prone to excessive adiposity. Identifying specific mechanisms that determine this susceptibility in at risk individuals is fundamental for finding appropriate remediation strategies. The pig is an excellent model for determining the effects of poor maternal nutrition because the gives birth to multiple piglets per delivery, both normal and nutrient restricted piglets. The piglet is also a better model for the study of fetal programming of adipose tissue because, unlike rodents that do not have substantial adipose tissue at birth, piglets are born with well-developed adipose tissue that can be sampled at birth for immediate analysis without the confounding effect of postnatal nutrition. Piglets and human infants display similar patterns of intestinal development, fat digestion and absorption (Miller and Ullrey, 1987), similar pathways of lipid and lipoprotein metabolism, and similar perinatal timing of the neural development, and similarity in essential nutrient requirements. Multiple experimental approaches will be used in the conduct of our investigations. These include well designed experiments to test the effects of multiple nutritional, management and genetic paradigms. Our expectation is that this work will provide critical information on the fundamental mechanisms that regulate developmental programming of adipose tissue.
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
3023510101010%
3023510102010%
3023510105010%
3023840101010%
3033510101010%
3033510102010%
3033510105010%
3053510101010%
3053840105010%
3073510105010%
Knowledge Area
303 - Genetic Improvement of Animals; 302 - Nutrient Utilization in Animals; 305 - Animal Physiological Processes; 307 - Animal Management Systems;

Subject Of Investigation
3840 - Laboratory animals; 3510 - Swine, live animal;

Field Of Science
1010 - Nutrition and metabolism; 1020 - Physiology; 1050 - Developmental biology;
Goals / Objectives
Excessive adipose tissue accretion leads to obesity in humans and poor efficiency of nutrient utilization in livestock. Factors that determine adipose tissue development are established early in development during prenatal and early post natal phases of growth. In order to stem the tide of obesity incidence and enhance animal growth it is critical to identify specific mechanisms that determine adipose tissue development early in development. The goal of this project is to: 1. Determine epigenetic mechanisms of prenatal programming of adiposity. 2. Determine the influence of prenatal environment (including determining the effects of genetic background, nutrition, and other physical factors) on postnatal development of adipose tissue. 3. Determine the effect of immediate postnatal nutrition on later adiposity.
Project Methods
Swine will be the animal model of choice in the conduct of proposed investigations on maternal and postnatal factors that affect adipose development. This is because the pig is an important agricultural animal and a good model of human disease. In some cases we will utilize cell culture and other animal models such as rats and mice. Experiments will be designed to test the various conditions that a fetus can experience during pregnancy and determine effects of these conditions on adipose tissue development. Some of these conditions include: 1. Maternal undernutrition. 2. Maternal overnutrition. 3. Maternal intake of specific nutrients such as proteins, calories, vitamins and minerals. 4. Maternal physical environment such as effect of temperature, exercise, spacing and handling. Offspring will be analyzed for their adipose tissue development. Effects of treatments on adipose tissue development will be compared for statistical significance with control animals that were kept in an ideal environment or fed ideal nutrition during pregnancy. In vitro models will attempt to replicate animal conditions using cell culture models. From these experiments it will be possible to determine the fundamental basis of prenatal and early postnatal conditions on adipose tissue development. This will be used to guide nutritional and management mitigation strategies that might be effective in preventing the adverse effects of suboptimal prenatal and postnatal experience on adipose development, health and overall welfare.

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

Outputs
Target Audience:Health professionals, graduate students, scienetists and corporate bodies, ordinary citizens. Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided?The project provided opportunity for several undergraduate and graduate students to get trained in hands-on laboratory techniques and in animal experimentation skills. Several grduate students attended national and international confereces whereresults of their experiments were presented. How have the results been disseminated to communities of interest?Results were desseminated through publication in scientific journals, attendance at scientific meetings and through popular press articles. What do you plan to do during the next reporting period to accomplish the goals? Nothing Reported

Impacts
What was accomplished under these goals? Research conducted in this project has led to new information information on the fundamental mechanisms that regulate developmental programming of adipose tissue. We have also decribed the impact of fiber on metabolic markers and obesity susceptibility. A major accomplishment of this proect is the discovery of effect of meternal obesity on offspring obesity. We found that maternal obesity results in an increase in expression of genes that promote adipocyte development in the offspring. This will ultimately increase obesity risk in the offspring.

Publications

  • Type: Journal Articles Status: Published Year Published: 2016 Citation: Zhang, Q., X. Chen, S.D. Eicher, K.M. Ajuwon, and T.J. Applegate. 2016. Effect of threonine deficiency on intestinal integrity and immune response to feed withdrawal combined with coccidial vaccine challenge in broiler chicks. Br. J. Nutr. 116:2030-2043.
  • Type: Journal Articles Status: Published Year Published: 2016 Citation: Adeola, O., Xue, P., A. J. Cowieson and K. M. Ajuwon. 2016. Basal endogenous losses of amino acids in protein nutrition research for swine and poultry. Anim. Feed. Sci. Tech. 221:274283
  • Type: Journal Articles Status: Published Year Published: 2017 Citation: 53. Huang. C.W., Y. J. Chen, J. T. Yang, C.Y. Chen, K.M. Ajuwon, S.E. Chen, N.W. Su, Y.S. Chen, H.J. Mersmann, and S.T. Ding. 2017. Docosahexaenoic acid increases accumulation of adipocyte triacylglycerol through up-regulation of lipogenic gene expression in pigs. Lipids Health Dis. 16(1):33
  • Type: Journal Articles Status: Published Year Published: 2017 Citation: 54. Lu, H., H. Yan, M. G. Ward, T. Stewart, O. Adeola, and K. M. Ajuwon. 2017. Effect on Rendement Napole (RN) genotype on metabolic markers in Ossabaw pigs fed different levels of fat. J. Anim. Physiol. Anim. Nutr. (Berl).doi: 10.1111/jpn.12720.
  • Type: Journal Articles Status: Published Year Published: 2017 Citation: Horn N, Miller G, Ajuwon KM, Adeola O. 2017. Garlic diallyl disulfide and diallyl trisulfide mitigates effects of pro-oxidant induced cellular stress and has immune modulatory function in LPS-stimulated porcine epithelial cells. J Anim Sci. 2017 Sep;95(9):4045-4051.
  • Type: Journal Articles Status: Published Year Published: 2017 Citation: Horn N, Miller G, Ajuwon KM, Adeola O. 2017. Ability of garlic-derived diallyl disulfide and diallyl trisulfide supplemented by oral gavage to mitigate effects of an acute postweaning feed and water deprivation event in nursery pigs. J Anim Sci. 2017 Aug;95(8):3579-3590. doi: 10.2527/jas.2017.1545


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

Outputs
Target Audience: Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided?The project has provided opportunity for several undergraduate and graduate students to get trained in hands-on laboratory techniques and in animal experimentation skills. How have the results been disseminated to communities of interest?The results have been disseminated through publications in scienentific journals, attendance at scientifc meetings and through popular press. What do you plan to do during the next reporting period to accomplish the goals?We want to investigate the effect of fiber on cellular membrane composition and how this is linked to obesity development and adipose tissue dysfunction.

Impacts
What was accomplished under these goals? We have described the impct of dietary fiber on obesity susceptibility and theimpact of fiber on the microbiome. This has been a major advance in our understanding of the factors that lead to excessive adipose tissue deposition.

Publications

  • Type: Journal Articles Status: Published Year Published: 2016 Citation: Stefanello, C., S.L. Vieira, P. Xue, K.M. Ajuwon and O. Adeola. 2016. Age-related energy values of bakery meal for broiler chickens determined using the regression method. Poult Sci. 95:1582-90. doi: 10.3382/ps/pew046.
  • Type: Journal Articles Status: Published Year Published: 2016 Citation: Chen, X., R. Murdoch, D.J. Shafer, K.M. Ajuwon and T.J. Applegate. 2016. Cytotoxicity of various chemicals and mycotoxins in fresh primary duck embryonic fibroblasts: a comparison to HepG2 cells. J. Appl. Toxicol. 36:1437-45. doi: 10.1002/jat.3298.
  • Type: Journal Articles Status: Published Year Published: 2016 Citation: Lu. H., A. Preynat, V. Legrand-Defretin, P. A. Geraert, O. Adeola and K.M. Ajuwon. 2016. Effects of dietary supplementation of exogenous multi-enzyme mixture containing carbohydrases and phytase on growth performance, energy and nutrient digestibility, and selected mucosal gene expression in the small intestine of weanling pigs fed nutrient deficient diets. Can. J. Anim. Sci. 96: 243-251, 10.1139/cjas-2015-0078.
  • Type: Journal Articles Status: Published Year Published: 2016 Citation: Lu, H., H. Yan, V. V. Almeida, O. Adeola and K. M. Ajuwon. 2016. Effects of dietary resistant starch content on nutrient and energy digestibility and fecal metabolomic profile in growing pigs. J. Anim. Sci. supplement 3: 364-368 doi:10.2527/jas.2015-9669
  • Type: Journal Articles Status: Published Year Published: 2016 Citation: Qu. H., H. Yan. H. Lu, S.S. Donkin and K.M. Ajuwon. 2016. Heat stress in pigs is accompanied by adipose tissue-specific responses that favor increased triglyceride storage. J. Anim. Sci. 94(5):1884-96. doi: 10.2527/jas.2015-0084.
  • Type: Journal Articles Status: Published Year Published: 2016 Citation: 1. Horn, N.L., F. Ruch, C.R. Little, G. Miller, K.M Ajuwon and O. Adeola. 2016. Determination of the adequate dose of garlic diallyl disulfide and diallyl trisulfide for effecting changes in growth performance, total-tract nutrient and energy digestibility, ileal characteristics, and serum immune parameters in broiler chickens. Poult Sci. 95:2360-5. doi: 10.3382/ps/pew126.
  • Type: Journal Articles Status: Published Year Published: 2016 Citation: 1. Xue, P., K.M. Ajuwon and O. Adeola. 2016. Phosphorus and nitrogen utilization responses of broiler chickens to dietary crude protein and phosphorus levels. Poult Sci. 95:2615-2623.
  • Type: Journal Articles Status: Published Year Published: 2016 Citation: Cowieson, A.J., H. Lu, K. M. Ajuwon, I. Knap and O. Adeola. 2016. Interactive effects of dietary protein source and exogenous protease on growth performance, immune competence and jejunal health of broiler chickens. Anim. Prod. Sci. http://dx.doi.org/10.1071/AN15523
  • Type: Journal Articles Status: Published Year Published: 2016 Citation: Ajuwon, K. M., E.J. Arentson-Lantz and S. S. Donkin. 2016. Excessive gestational calorie intake in sows regulates early postnatal adipose tissue development in the offspring. BMC Nutrition 2:29.
  • Type: Journal Articles Status: Published Year Published: 2015 Citation: Yan, H. and K.M. Ajuwon. 2015. Mechanism of butyrate stimulation of triglyceride storage and adipokine expression during adipogenic differentiation of porcine stromovascular cells. PLoS One. 29;10(12):e0145940. doi: 10.1371/journal.pone.0145940.
  • Type: Journal Articles Status: Published Year Published: 2016 Citation: 1. Huang, C.W., Y.S. Chien, Y.J. Chen, K.M. Ajuwon, H.M. Mersmann and S.T. Ding ST. 2016. Role of n-3 Polyunsaturated Fatty Acids in Ameliorating the Obesity-Induced Metabolic Syndrome in Animal Models and Humans. Int J Mol Sci. 17(10). pii: E1689.


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

Outputs
Target Audience:Our study is aimed at livestock industry professionals or technical experts, farmers, students and scholars and the general public. This broad target audience allows wide and effective dissemination of research findings. Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided?1. We have hired twonew undergrduate students to work on teh project. 2. Two graduate students were sent toconferences to present their research findings. How have the results been disseminated to communities of interest?Yes. Results have been shared with academic colleagues and graduate students. What do you plan to do during the next reporting period to accomplish the goals?We plan to continue to investigate fundamental mechanims of adipocyte response to heat stress and the role of calcium. We also hope to continue to investigate effect of heat stress on membrane fluidity and adipose tissue fatty acid composition.

Impacts
What was accomplished under these goals? 1. We have discovered that increased glyceroneogeneis is a major evewnt in adipocyte response to heat stress. 2. Calcium plays a major role in adipocyte response to heat stress. This is because adipocytes undergoing heat stress have a higher calcium release from teh endoplasmic reticulum in response to ionomycin stimulation. 3. The heat sensing receptots TRPV1 and TRPV3, play major roles in heat stress response in adipocytes.

Publications

  • Type: Journal Articles Status: Published Year Published: 2015 Citation: Qu H, Donkin SS, Ajuwon KM. Heat stress enhances adipogenic differentiation of subcutaneous fat depot-derived porcine stromovascular cells.J Anim Sci. 2015 Aug;93(8):3832-42
  • Type: Journal Articles Status: Published Year Published: 2015 Citation: Shih CL, Ajuwon KM. Inhibition of MMP-13 prevents diet-induced obesity in mice and suppresses adipogenesis in 3T3-L1 preadipocytes.Mol Biol Rep. 2015 Jul;42(7):1225-32. doi: 10.1007/s11033-015-3861-2
  • Type: Journal Articles Status: Accepted Year Published: 2016 Citation: 2. Horn, N., F. Ruch, G. Miller, K.M. Ajuwon, and O. Adeola. 2015. Expression of cytokine and tight junction genes and ileal mucosal morphology in nursery pigs in response to garlic diallyl disulfide and diallyl trisulfide compounds. In press.
  • Type: Journal Articles Status: Accepted Year Published: 2016 Citation: Yan, H, H.Lu, V. V. Almeida, M. G.Ward, O. Adeola, C. H. Nakatsu and K. M. Ajuwon. Effects of dietary resistant starch content on metabolic status, milk composition, and microbial profile in lactating sows and on offspring performance. JAPAN, 2016, In press.
  • Type: Journal Articles Status: Awaiting Publication Year Published: 2016 Citation: Ajuwon. K.M. Towards a better understanding of mechanisms of probiotics and prebiotics action in poultry species. 2016. JAPR in press


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

Outputs
Target Audience: Target audiences reached included farmers, scientists, students (graduate and undergraduate) andentrepreneurs. Minority students reached included African Americans, Latinos and Asians. Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided? This projects has provided opportunities to demonstrate models of maternalover-nutritionin the pig model and its effectson the metabolic status on the offspring. How have the results been disseminated to communities of interest? Yes: nutritionists andgraduate students What do you plan to do during the next reporting period to accomplish the goals? Continue to fine-tune our model of fetal and maternal nutrition. Determine effects of the environment on fetal programming

Impacts
What was accomplished under these goals? A major impact of our study in the reporting year is the effect that maternalover-nutritionhas on the expression of gluconeogenic and adipogenic genes in the offspring of dams that were exposed toover-nutritionduring gestation. From these studies wewere able to establish that maternalover-nutritionincreased the expression of PGC-1, a major gene regulating energy homeostatis, in the intestine. In addition offspring of dams exposed toover-nutritionhad increased expression of genes such as PPAR gamma, PCK1 and adipokines such as leptin andadiponectin. This means thatover-nutritionin pregnant mothers can have significant effect on the metabolism of their offspring after birth.

Publications

  • Type: Journal Articles Status: Published Year Published: 2014 Citation: Ajuwon KM.Chronic immune stimulation in adipose tissue and its consequences for health and performance in the pig. Vet Immunol Immunopathol. 2014 Jun 15;159(3-4):166-70.
  • Type: Journal Articles Status: Published Year Published: 2014 Citation: Arentson-Lantz EJ, Buhman KK, Ajuwon K, Donkin SS. Excess pregnancy weight gain leads to early indications of metabolic syndrome in a swine model of fetal programming. Nutr Res. 2014 Mar;34(3):241-9.
  • Type: Journal Articles Status: Published Year Published: 2014 Citation: Horn N, Ruch F, Miller G, Ajuwon KM, Adeola O. Impact of acute water and feed deprivation events on growth performance, intestinal characteristics, and serum stress markers in weaned pigs. J Anim Sci. 2014 Oct;92(10):4407-16.


Progress 10/01/12 to 09/30/13

Outputs
Target Audience: 1. Students, including minority students. 2. Veterinarians 3. Academic colleagues 4. Industry partners in animal feed and pig growing business Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided? The project has provided traning opportunities fro four graduate students in teh reporting year. In addition two undergraduate students worked on several aspects of teh project in the reporting year. This provided training opportuity for them to acquire skills in the handling of samples for molecular biology analysis. Graduate students on the project continue to improve their understanding of metabolism. They are able to present their work at multiple conferences in the reporting year. How have the results been disseminated to communities of interest? Iinformation was disseminated at multiple conference meetings (Joint Annual Animal Sciences meeting andExperimental Biology meeting)and during private sessions with students, colleagues and industry stakeholders. What do you plan to do during the next reporting period to accomplish the goals? We plan to continue our work on the impact of maternal nutrition on programming of postnatal growth and body composition. We also plan to continue to investigate the role of AMPK on metabolism in adipose tissue using the unque pig genetic backgrounds that we have generated. In the coming year, we plan to investigate the role of heat stress on adipose tissue metabolism with respoect to bosy fat accretion drung heat stress in pigs. This will help generate information that may be useful in developing mitigating strategies against the negativeeffects of heat stress in pigs.

Impacts
What was accomplished under these goals? New knowledge on the role of volatile fatty acids, such as butyrate, on metabolism in the whole body, especiually in the adipose tissue, was created. Additionally, we expanded information on the role of AMPKgenetic background on metabolism and body composition of pigs from activities conducted in the reporting year. New information on the role of transforming growth factor รพ on adipocyte differentiation and its consequence for lipid accretion in animals and human obesity was obtained. This critical information was disseminated at conference meetings and during private sessions with students, colleagues and industry stakeholders.

Publications

  • Type: Journal Articles Status: Published Year Published: 2013 Citation: 1) Lu*, H., S.A. Adedokun, A. Preynat, V. Legrand-Defretin, P. Geraert, O. Adeola, and K. M. Ajuwon*.2013. Impact of exogenous carbohydrases and phytase on growth performance and nutrient digestibility in broilers. Can. J. Anim. Sci. 93: 243-249
  • Type: Journal Articles Status: Published Year Published: 2013 Citation: 2) Olukosi*, O.A., C. Kong, F. Fru-Nji, K. M. Ajuwon, and O. Adeola* 2013. Assessment of the efficacy of a 6-phytase and its effects on molecular markers for intestinal inflammation response mucin secretion and phosphate transport in broiler chickens. Poult. Sci 2013 92(8):2101-8
  • Type: Journal Articles Status: Awaiting Publication Year Published: 2013 Citation: Lu*, H, S.A. Adedokun, O. Adeola and K. M. Ajuwon*. 2013. Anti-inflammatory effects of non-antibiotic alternatives in an experimental model of coccidia challenge in broiler chickens. J. Poult. Sci
  • Type: Journal Articles Status: Published Year Published: 2013 Citation: Lu*, H., M.G. Ward, O. Adeola and K.M. Ajuwon*. 2013. Regulation of adipocyte differentiation and gene expression-crosstalk between TGF? and wnt signaling pathways. Mol Biol Rep. 2013 40(9):5237-45
  • Type: Journal Articles Status: Published Year Published: 2013 Citation: 5) Hui*, Y., R. Potu, H. Lu, V. V. Almeida, T. Stewart, D. Ragland, A. Armstrong , O. Adeola, C. H. Nakatsu and K. M. Ajuwon*. 2013. Dietary fat content and fiber type modulate hind gut microbial community and metabolic markers in the pig. PLoS One. PLoS One. 2013; 8(4):e59581
  • Type: Journal Articles Status: Published Year Published: 2013 Citation: 6) Potu*,R.B., H. Lu, O. Adeola and K.M. Ajuwon*. 2013. Metabolic markers in Ossabaw pigs fed high fat diets enriched in regular or low alpha-linolenic acid soy oil. Nutrition & Metabolism. 10:27. doi:10.1186/1743-7075-10-27
  • Type: Journal Articles Status: Published Year Published: 2013 Citation: 7) Schinckel*, A.P., M.E. Einstein, K.M. Ajuwon and O. Adeola*. 2013. Characterization of whole body compositional growth of male ducks during the twenty-nine days post-hatch period,. Can. J. Anim. Sci. 93: 113-122.
  • Type: Journal Articles Status: Published Year Published: 2012 Citation: 8) Lu*, H., Su, S and K.M. Ajuwon*. 2012. Butyrate supplementation to gestating sows and piglets induces muscle and adipose tissue oxidative genes and improves growth performance. J Anim. Sci. 90 Suppl 4:430-2.


Progress 10/01/11 to 09/30/12

Outputs
OUTPUTS: Several experiments were conducted within the reporting year. These include: 1. Investigating the role of fiber in the regulation of cecal microbial community in the pig: The experiment was aimed at investigating the effects of different fiber types, chosen based on fermentability, on pig hind gut microbial community. Pigs were either inulin or cellulose-based fiber at 4% of the diet for 8 weeks. 2. The role of AMPK genotype in the response to a high fat diet in the pig. This experiment was conducted to investigate the importance of AMPK status of growing pigs during high fat diet feeding. Animals of either the wild type or mutated AMPK genotypes were fed a 15% fat diet for 8 weeks and the level of back fat, expression of key metabolic genes and concentrations of key serum metabolites were investigated. 3. Fetal programming of adipose tissue metabolism. We investigated the role of maternal nutrition and birth weight on adipose tissue programming. Dissemination activities included attendance at major conferences which included Experimental Biology (April 21-25, 2012 - San Diego) and American Society of of Animal Sciences (July 15-19, 2012, Phoenix) annual meetings. Outreach activities include establishment of collaborations with Dr. Ormond MacDougald (University of Michigan) and Dr. Refetof at the (University of Chicago). PARTICIPANTS: 1. Hang Lu, Purdue University 2. Hui Yan, Purdue University 3. Ramesh Potu, Purdue University 4. Michelle Chia-Li Shih, Purdue University TARGET AUDIENCES: 1. Students, includig minority students. 2. Veterinarians 3. Academic colleagues 4. Industry partners in animal feed and pig growing business PROJECT MODIFICATIONS: Not relevant to this project.

Impacts
New knowledge of the role of fiber in the regulation of cecal microbial community in the pig was created. Additionally, knowledge on the role of AMPK gene on metabolism and body composition of pigs was created as a result of activities conducted in the reporting year. Furthermore, knowldge was also generated on the impact of maternal status during gestation on the metabolic status of offspring and effect on growth performance. This critical information was disseminated at conference meetings and during private sessions with students, colleagues and industry stakeholders.

Publications

  • 1. Ward MG, Ajuwon KM.Biglycan Deletion Alters Adiponectin Expression in Murine Adipose Tissue and 3T3-L1 Adipocytes. PLoS One. 2012;7(11):e50554. doi: 10.1371/journal.pone.0050554. Epub 2012 Nov 26.
  • 2.Banz WJ, Strader AD, Ajuwon KM, Hou Y, Meyers CY, Davis JE.(+)-z-bisdehydrodoisynolic Acid enhances Basal metabolism and Fatty Acid oxidation in female obese zucker rats. J Obes. 2012;2012:154145. doi: 10.1155/2012/154145.
  • 3.Adapala VJ, Ward M, Ajuwon K.Adipose tissue biglycan as a potential antiinflammatory target of sodium salicylate in mice fed a high fat diet. J Inflamm (Lond). 2012 Apr 25;9(1):15.
  • 4.Adedokun SA, Ajuwon KM, Romero LF, Adeola O.Ileal endogenous amino acid losses: response of broiler chickens to fiber and mild coccidial vaccine challenge.Poult Sci. 2012 Apr;91(4):899-907. doi: 10.3382/ps.2011-01777.
  • 5.Adapala VJ, Adedokun SA, Considine RV, Ajuwon KM.Acute inflammation plays a limited role in the regulation of adipose tissue COL1A1 protein abundance.J Nutr Biochem. 2012 Jun;23(6):567-72.
  • 6.Olayiwola Adeola, Allan P. Schinckel, Kolapo M. Ajuwon, Mark E. EinsteinAccretion Rates and Efficiency of Amino Acid Utilization during the Twenty-nine Days Post-Hatch Period in Male Ducks. The Journal of Poultry Science Vol. 49 (2012) No. 2.


Progress 10/01/10 to 09/30/11

Outputs
OUTPUTS: Outputs from our findings on the role of extracellular matrix proteins in adipogenesis was shared with scientists and stakeholders at multiple conferences in 2011: (1) At the world poultry scientiifc forum in Atlanta, in Januay 2011. (2) At the Experimental Biology meeting in Washington DC in April (3) At the American Society for Animal Sciences meeting in New Oleans in July. PARTICIPANTS: 1. Robert Considine,Indiana University School of Medicine 2. Michael Sturek, Indiana University School of Medicine 3. Jitendra Adapala, Purdue University 4. Ramesh Potu, Purdue University 5. Meliza Ward, Purdue University 6. Hang Lu, Purdue University 7. Chia-Li Shih, Purdue Univerity TARGET AUDIENCES: Several meetings with scentists and farmers and other stakeholders physically and through phone conversations. PROJECT MODIFICATIONS: Nothing significant to report during this reporting period.

Impacts
New fundamental knowledge on the role of extracellular matrix proteins in adipose tissue development was obtained. This increased knowledge will guide decision making on nutritional approaches for preventing obesity and in optimizing animal productivity. Eventually, application of this knowledge will lead to lowering obesity rates and improved nutrition and health of the American people.

Publications

  • 1. Adapala VJ, Adedokun SA, Considine RV, Ajuwon KM.Acute inflammation plays a limited role in the regulation of adipose tissue COL1A1 protein abundance. J Nutr Biochem. 2011 Jul 18. [Epub ahead of print]
  • 2.Ward M, Ajuwon KM.Regulation of pre-adipocyte proliferation and apoptosis by the small leucine-rich proteoglycans, biglycan and decorin. Cell Prolif. 2011 44(4):343-51
  • 3.Adapala VJ, Buhman KK, Ajuwon KM. Novel anti-inflammatory role of SLPI in adipose tissue and its regulation by high fat diet. J Inflamm (Lond). 2011 Feb 28;8:5


Progress 10/01/09 to 09/30/10

Outputs
OUTPUTS: Several experiments were conducted in the reporting year: 1. Role of biglycan in adipose tissue development and inflammation. This study was conducted using biglycan knock out and wild type mice to determine the effects of biglycan in adipose tissue develpment and insulin resistance. Animals were placed on either normal chow or a high fat diet for 10 weeks. The results show that mice lacking biglycan had reduced serum insulin concentration when placed on high fat diet. 2. Role of yeast products in protection against inflammation induced by coccidiosis. This experiment was conducted with the objective of determining the efficacy of yeast products in combating immune stimulation by coccidia. The results show that yeast products downregulate inflammatory response by coccidia and enhance metabolizable energy availability in broilers. 3. The Ossabaw pig model of metabolic syndrome; Ossabaw pigs were put on either a normal low fat diet on 2 high fat diets, one with a high concentration of hydrogenated oil and one with low-linolenic soybean oil. Diest with low-lin oil led to normal blood slucose whereas those with hydrogenated oil had elevated blood glucose. Attended the Experimental Biology confernce in Anaheim (April 24-28), ASAS meeting in Denver (Jul 7-10), and World poultry Expo in Atlanta (Jan 27-29) PARTICIPANTS: Jitendra Adapala Meliza Ward Ramesh Potu Adedokun Adetayo Kola Ajuwon Hang Lu Collaborators: Mike Sturek, Indiana University School of Medicine TARGET AUDIENCES: Indiana Pork Board, scientists, students, Indiana Soybean Association PROJECT MODIFICATIONS: Not relevant to this project.

Impacts
New knowledge: 1.We have a better knowledge of the role of extracellular matrix protein biglycan in adipose tissue dysfunction. 2. Low linolenic soybean oil prevents hyperglycemia and hence will have health benefit when it replaces hydrogenated soyben oil commonly used in cooking and confectionary products. 3. When used ahead of an infection, yeast products can confer immune resistance against enteric diseases.

Publications

  • Meliza Grace Ward, Jitendra Adapala, Sunday Adedokun, and Kolapo Ajuwon. 2010 Dynamic changes in extracellular matrix gene regulation in adipose tissue and impact on preadipocyte proliferation and apoptosis FASEB J April 6, 24:341.1
  • Venkata Jitendra Kumar Adapala, Sunday Adetayo Adedokun, Olayiwola Adeola, Meliza G Ward, and Kolapo Matthew Ajuwon. 2010. Potential Role of Toll-like Receptor 4 in Obesity-Induced Adipose Tissue Remodeling FASEB J April 6, 24:341.3


Progress 10/01/08 to 09/30/09

Outputs
OUTPUTS: Multiple experiments and activities were conducted during the reporting year: (1) Extracellular Matrix (ECM) Changes in Adipose Tissue - Although adipose tissue is known to expand to store excess calories, it undergoes tremendous remodelling details of which are unclear. Therefore, we conducted detailed analyses of ECM changes in adipose tissue in animal fed a high fat diet. (2) Regulation of Inflammation by fatty acid- We also conducted experiments to determine how macrophages respond to different fatty acds. We used the RAW 264.7 macrophage cell line and treated them with fatty acids bound to BSA. (3) Conferences - Attended the following conferences: (i)US Poultry and Egg Association. International Poultry Show, Atlanta, Georgia,1/28-1/29, 2009 (ii) 42nd Midwest Sectional Scientific Sessions. ASAS, 3/16-3/18, 2009, Des Moines, Iowa. (iii) 2009 Experimental Biology Meeting,April 18-22, 2009. (iv)17th European Poultry Nutrition Symposium Edinburgh, Scotland, 8/23-8/27, 2009 (4) Teaching - Taught ANS 595 (Adipose Biology) course in the spring of 2009 PARTICIPANTS: Principal Investigator: Kolapo Ajuwon Collaborators: Robert Considine, Gatch Clinical Building, Room 455 541 N. Clinical Dr. Indianapolis, IN 46202-5111 Mike Sturek, Department of Cellular & Integrative Physiology Indiana University School of Medicine 635 Barnhill Drive, Room 385 Indianapolis, Indiana 46202-5120 Technician: Stephanie Koser Post Doctoral Associate: Adetayo Adedokun Graduate Students: (1) Meliza Ward (2) Adapala Jitendra (3)Ramesh Babu TARGET AUDIENCES: Target Audiences- Scientists, nutritionsits, farmers, students Efforts- Taught ANS 595, Adipose Biology course to students. PROJECT MODIFICATIONS: Not relevant to this project.

Impacts
Obesity and ECM - We observed significant and previuosly uncharacterized changes in adipose tissue ECM in obesity. In addition some of these changes are significantly associated with changes in markers of inflammation and insulin sensitivity. Therefore, ECM componenets could have previously unrecognized role in the regulation of inflamation in adipose tissue which may be connected with induction of insulin resistance Fatty acids and Inflammation - We found that fatty acids, depending on their degree of saturation, might be responsible for the induction of matrix degrading enzymes known as matrix metalloproteases in adipose tissue.

Publications

  • Hausman, G.J.*, M.V. Dodson*, K. Ajuwon*, M. Azain*, K.M. Barnes*, L.L. Guan*, Z. Jiang*, S.P. Poulos*, R.D. Sainz*, S. Smith*, M. Spurlock*, J. Novakofski*, M.E. Fernyhough* and W.G. Bergen*. 2009. Board Invited Review: The biology and regulation of preadipocytes and adipocytes in meat animals. J. Anim. Sci. 87:1218-1246.
  • Ajuwon, K.M.*, B. William and T.A. Winters. 2009. Stimulation with peptidoglycan Induces interleukin 6 and TLR2 Expression and a concomitant downregulation of expression of adiponectin receptors 1 and 2 in 3T3-L1 adipocytes. J. Inflamm (Lond). 6(1):8.


Progress 10/01/07 to 09/30/08

Outputs
OUTPUTS: Obesity, resulting from excessive adipose tissue deposition in humans continues to be a major drag on the economy. About 30% of adult American population are now classified as obese or overweight. Utilization of nutrients for fat deposition is also a major cause of reducion in animal performance and profits in livestock production. Our main objective in the first year of this project was to establish our model system. We studied the regulation of proteoglycans in in vitro model of adipocyte differentiation and in pigs on control (low fat) and a high fat diet. First, we found that adipocyte differentiation is accompanied by reduction in the mRNA abundance of proteoglycans, decorin and biglycan. After induction of adipogenesis, the mRNA expression of both proteoglycans falls precipitously to about 10% of the level at confluence. This reduced level of expression was noticeable 2 days after adipogenic induction and was sustained until day 4, after which the expression level begins to rise. Nevertheless, the expression at day 12 remains at approximately 50% of the level at confluence.In addition, expression of both proteoglycans was significantly reduced in pigs on the high fat diet. A seminar was presented by Dr. Ajuwon to the Purdue Ingestive Behavior Research Center advisory commitee on the role of extracellular matrix in adipose development. PARTICIPANTS: Tayo Adedokun, PhD. Postdoctoral Research Associate Jitendra Adapala, graduate student Meliza Cruz, graduate student Kara Felix, undergraduate student TARGET AUDIENCES: Nutritionists, Physicians, Swine geneticists PROJECT MODIFICATIONS: Not relevant to this project.

Impacts
Because both decorin and biglycan are differentially regulated during adipogenesis, they could play significant regulatory roles in adipogenesis and obesity. Consideration is being given to developing tissue expression levels of these proteoglycans as indicators of inflammation and insulin resistance in adipose tissue. They could also be used as indicators of feed efficiency in pigs.

Publications

  • No publications reported this period