Progress 10/01/14 to 09/30/18
Outputs
Target Audience:The target audience includes researchers who study bone physiology, obesity and inherited metabolic disorders; manufacturers of medical foods for humans and experimental diets for animals; and individuals who have metabolic diseases that require consumption of amino acid formulas. Changes/Problems:
Nothing Reported
What opportunities for training and professional development has the project provided?PhD student Bridget Stroup was supported by this Hatch grant and finished her degree in 2017. Bridget presented an oral workshop on bone health in PKU at the Genetic Metabolic Dietitians International meeting in Orlando, FL on April 27, 2018. How have the results been disseminated to communities of interest?Denise Ney gave invited presentations regarding the impact of dietary glycomacropeptide on bone and renal health at the following meetings: Society for Inherited Metabolic Disorders in San Diego, CA on March 12, 2018; National Academy of Sciences Workshop in Washington D.C. on April 2, 2018; Genetic Metabolic Dietitians International in Orlando, FL on April 25, 2018; Metabolic Clinicians in Buenos Aires, Argentina on June 3, 2018; and National PKU Alliance in Atlanta, GA on July 7, 2018. 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 for Goal 1 was accomplished for male and female phenylketonuria (PKU) and wild type (WT) mice fed a low-acid buffered amino acid (BAA) diet compared with a high-acid AA diet, a glycomacropeptide (GMP) diet, and a casein diet. We extended the goal to examine both bone and renal status with the final year of the project. A manuscript is in preparation and will be submitted in 2019. Both female and male PKU mice showed poor bone status based on significant reductions in bone mineral content and bone strength compared to WT mice. The decline in bone status was greater in female PKU compared to male PKU mice. Buffering the AA diet did not change bone status in either PKU or WT mice. Thus, in the context of an AA-based diet, dietary acid load is not a primary determinant of low bone mineral content in PKU mice. Renal response to the dietary treatments differed in male and female mice. Male PKU and WT mice fed the high-acid AA diet showed an increase in renal mass and mild cortical tubular vacuolation located in the proximal tubules, whereas male mice fed the casein, BAA and GMP diets had absent-minimal tubular vacuolation. Notably, cortical tubular vacuolation was absent in all female WT and PKU mice. Mild medullary tubular dilation and proteinosis were observed in male PKU and WT mice fed the AA and BAA diets, and in PKU male mice fed the casein diet. Female PKU mice fed AA, BAA, or GMP diets demonstrated moderate medullary tubular dilation compared to WT mice fed the casein diet. Polyuria, a symptom of renal dysfunction, was present in both male and female PKU mice fed the AA and BAA diets; this is consistent with the observed renal histopathology. Thus regardless of dietary acid load, chronic intake of amino acids may lead to renal dysfunction as evidenced by medullary tubular dilation and proteinosis, polyuria, and increased renal mass in male WT and PKU male mice.
Publications
- Type:
Theses/Dissertations
Status:
Published
Year Published:
2017
Citation:
Bridget M. Stroup. Nutritional management of phenylketonuria with glycomacropeptide medical foods. The University of Wisconsin - Madison, 2017. Ann Arbor: ProQuest. Web. 21 Nov. 2017.
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Progress 10/01/16 to 09/30/17
Outputs
Target Audience:The target audience includes researchers who study bone physiology, obesity and inherited metabolic disorders; manufacturers of medical foods for humans and experimental diets for animals; and individuals who have metabolic diseases that require consumption of amino acid formulas. Changes/Problems:
Nothing Reported
What opportunities for training and professional development has the project provided?PhD student Bridget Stroup is supported by this Hatch project.Bridgetreceived her PhDAugust 2017. Bridget presented abstracts at the 2017 Society for the Study of Inborn Errors of Metabolism in Rome, Italy and gave a presentation to practicing metabolic dietitians in Columbus, OH. These abstracts and presentationsincluded data from human PKU subjects as well as mice, as supported by this Hatch grant. How have the results been disseminated to communities of interest?Bridget's PhD dissertation was published and a press release was issued by the University of Wisconsin-Madison University Communications website on 12/21/17 https://news.wisc.edu/new-clues-to-healthy-bones-for-those-with-pku/ and college publication, GROW https://grow.cals.wisc.edu/tag/grow-fall-2017 What do you plan to do during the next reporting period to accomplish the goals?During the next reporting period, we will complete analysis of the dataset fromwild type andphenylketonuriamice fed amino acid, casein and glycomacropeptide diets with different levels of dietary acid. We will complete analysis of renal net acid excretion and bone composition in this dataset and submit a paper for publication in 2018.
Impacts
What was accomplished under these goals?
We established that female C57Bl/6 mice feda high-fatdiet compared with alow-fat diet show a bone phenotype where femora show increased bone mineral density, but bone quality deteriorates resulting in brittle bones. This observation occured independent of a dietary protein source of either glycomacropeptideor casein. Our datademonstrate the detrimental effects of obesity induced by high fat feeding on bone health. We show that mice fed a low-fat glycomacropeptide diet demonstrate increased total body fat-free or leanmass and total body mineralization with the benefit of reduced femoral brittleness compared with a low-fat casein diet. Taken together, these data support the ability of glycomacropeptide to improve bone health and reduce body fat content with relevance to the prevention and treatment of osteoporosis and obesity in women.We wrote a review paper to share our findings and submitted two federal grants (not funded to date)to extend our research by conducting studies in female human subjects and individuals with phenylketonuriafed glycomacropeptide.
Publications
- Type:
Journal Articles
Status:
Published
Year Published:
2017
Citation:
Ney DM and Etzel MR. Designing medical foods for inherited metabolic disorders: why intact protein is superior to amino acids. Curr Opin Biotechnol 44:39-45, 2017. www.sciencedirect.com
- Type:
Theses/Dissertations
Status:
Published
Year Published:
2017
Citation:
Stroup, Bridget M. "Nutritional Management of Phenylketonuria with Glycomacropeptide Medical Foods." The University of Wisconsin - Madison, 2017. Ann Arbor: ProQuest.
https://search.proquest.com/docview/1937562835?pq-origsite=gscholar
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Progress 10/01/15 to 09/30/16
Outputs
Target Audience:The target audience includes researchers who study bone physiology, obesity and inherited metabolic disorders; manufacturers of medical foods for humans and experimental diets for animals; and individuals who have metabolic diseases that require consumption of amino acid formulas. Changes/Problems:
Nothing Reported
What opportunities for training and professional development has the project provided?PhD student Bridget Stroup is supported by this Hatch project. She is a co-author on the PLoS ONE manuscript and will finish her PhD in 2017.Bridget presented abstracts at the 2016 meetings of Genetics Metabolic Dietitians International, the National PKU Alliance and the Society for the Study of Inborn Errors of Metabolism. These abstracts included data from human PKU subjects as well as mice, as supported by this Hatch grant. Emily Sawin, supported by my earlier Hatch grant completed her PhD June 2016. How have the results been disseminated to communities of interest?A paper was published in PLoS ONE and an invited review was published in Current Opinion in Biotechnology, as noted under publications. Denise Ney gave invited presentations regarding glycomacropeptide and bone health at the following meetings: Genetic Metabolic Dietitians International in Scottsdale, Arizona on April 26, 2016; Davisco Foods International, Eden Prairie, Minnesota on June 14, 2016; National PKU Alliance in Indianapolis, Indiana on July 28, 2016; and the Society for the Study of Inborn Errors of Metabolism in Rome, Italy on September 4, 2016. What do you plan to do during the next reporting period to accomplish the goals?During the next reporting period, we will complete analysis of the dataset from female mice fed casein and glycomacropeptide diets where after induction of obesity by feeding high-fat feeding for 7 months, mice were switched to low-fat diets to induce weight loss. We will compare how weight loss induced by feeding low-fat diets comprising glycomacropeptide or casein affected body composition, fat oxidation and bone status including assessment of femoral biomechanical performance. A paper will be submitted with these data in 2017.
Impacts
What was accomplished under these goals?
Impacts for goals 1 and 2 include: We have established that female C57Bl/6 mice fed either high-fat or low-fat diets with glycomacropeptide compared with casein demonstrate improved bone status as reflected in increased total body bone mineral content and femur length. We also demonstrate that chronic ingestion of a high-fat diet with either glycomacroprotein or casein as the protein source induces a bone phenotype where femora show increased bone mineral density, but bone quality deteriorates resulting in brittle bones. We have established that female C57Bl/6 mice fed a high-fat glycomacropeptide diet demonstrate increased fat oxidation capacity in subcutaneous fat compared with mice fed a high-fat casein diet. We also demonstrated that mice fed a low-fat glycomacropeptide diet demonstrate increased total body fat-free mass and mineralization with the benefit that the brittleness of femora is reduced compared with a low-fat casein diet. Taken together, these data support the ability of glycomacropeptide to improve bone health and reduce body fat content with relevance to the prevention and treatment of osteoporosis and obesity in women.
Publications
- Type:
Journal Articles
Status:
Published
Year Published:
2016
Citation:
Sawin EA, Stroup BM, Murali SG, ONeill LM, Ntambi JM, and Ney DM. 2016. Differential effects of dietary fat content and protein source on bone phenotype and fatty acid oxidation in female C57Bl/6 mice. PLoS ONE 11(10): e0163234. doi:10.1371/journal.pone.0163234
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Progress 10/01/14 to 09/30/15
Outputs
Target Audience:The target audience includes researchers who study bone physiology, obesity and inherited metabolic disorders, manufacturers of medical foods for humans and experimental diets for animals, and individuals who have metabolic diseases that require consumption of amino acid formulas. Changes/Problems:
Nothing Reported
What opportunities for training and professional development has the project provided?PhD student Bridget Stroup is being supported by this Hatch project. She has learned the methodology for assessing the biomechanical properties of bone during the past year and is maintaining our PKU mouse colony. Bridget passed her research proposal exam and has achieved dissertator status. She attended the Experimental Biology 2015 meeting and presented an abstract that included data from human PKU subjects as well as mice. How have the results been disseminated to communities of interest?A paper was published in Am J Physiol as noted under Products. Denise Ney gave invited presentations to the Canadian PKU Association in Saskatoon, Canada on April 11, 2015 and to the Portugese Society of Metabolic Disorders in Porto, Portugal March 19, 2015. The topic of both presentations was the efficacy of GMP in the PKU diet with discussion of the advantages of GMP for bone health. What do you plan to do during the next reporting period to accomplish the goals?During the next reporting period, we will complete the analysis of the dataset to characterize the biomechanical properties of femora from mice fed defined GMP, casein and AA diets. We will also complete analysis of changes in hormonal profiles and body composition from these mice. Additional studies to characterize the effects of high-fat diets on the intestinal microbiome in mice fed GMP and casein diets are planned. Histological evaluation of enlarged kidneys from mice fed AA and control diets is planned. A paper will be submitted with some of these data in summer 2016.
Impacts
What was accomplished under these goals?
Accomplishments for goals 1 and 2 include: 1. We have established higher bone mineral content in female C57Bl/6 mice fed GMP compared with casein diets. Femora bones from these mice have been subjected to the 3-point bending test to assess the biomechanical properties of the bones. These data for biomechanical performance are currently being analyzed. We have determined that renal net acid excretionis reduced in mice fed a buffered AA diet compared with a control AA diet. 2. We have determined that female C57Bl/6 mice fed GMP compared with casein diets have increased fat oxidation in subcutaneous fat and higher fat free mass.We have also assessed the cecal intestinal microbiota and determined that GMP is a prebiotic with anti-inflammatory effects which could help explain the positive effects of GMP on bone mass.
Publications
- Type:
Journal Articles
Status:
Published
Year Published:
2015
Citation:
Sawin EA, DeWolfe TJ, Aktas B, Stroup BM, Murali SG, Steele JL and Ney DM. Glycomacropeptide is a prebiotic that reduces Desulfovibrio bacteria, increases cecal short-chain fatty acids, and is anti-inflammatory in mice. Am J Physiol Gastrointest Liver Physiol 309:G590-G601, 2015.
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