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Restriction of essential amino acids dictates the systemic metabolic response to dietary protein dilution.
Yap, Yann W; Rusu, Patricia M; Chan, Andrea Y; Fam, Barbara C; Jungmann, Andreas; Solon-Biet, Samantha M; Barlow, Christopher K; Creek, Darren J; Huang, Cheng; Schittenhelm, Ralf B; Morgan, Bruce; Schmoll, Dieter; Kiens, Bente; Piper, Matthew D W; Heikenwälder, Mathias; Simpson, Stephen J; Bröer, Stefan; Andrikopoulos, Sofianos; Müller, Oliver J; Rose, Adam J.
Affiliation
  • Yap YW; Department of Biochemistry and Molecular Biology, Metabolism, Diabetes and Obesity Program, Biomedicine Discovery Institute, Monash University, Clayton, VIC, 3800, Australia.
  • Rusu PM; Department of Biochemistry and Molecular Biology, Metabolism, Diabetes and Obesity Program, Biomedicine Discovery Institute, Monash University, Clayton, VIC, 3800, Australia.
  • Chan AY; Department of Biochemistry and Molecular Biology, Metabolism, Diabetes and Obesity Program, Biomedicine Discovery Institute, Monash University, Clayton, VIC, 3800, Australia.
  • Fam BC; Department of Medicine (Austin Health), University of Melbourne, Heidelberg, VIC, 3084, Australia.
  • Jungmann A; Department of Internal Medicine III, University Hospital Heidelberg, Heidelberg, Germany.
  • Solon-Biet SM; German Center for Cardiovascular Research (DZHK), Partner sites Kiel and Heidelberg, Germany.
  • Barlow CK; Charles Perkins Centre, School of Life and Environmental Sciences, University of Sydney, Sydney, NSW, Australia.
  • Creek DJ; Biomedical Proteomics and Metabolomics Facility and the Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, VIC, 3800, Australia.
  • Huang C; Biomedical Proteomics and Metabolomics Facility and the Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, VIC, 3800, Australia.
  • Schittenhelm RB; Monash Institute of Pharmaceutical Sciences, Monash University, Melbourne, VIC, 3052, Australia.
  • Morgan B; Biomedical Proteomics and Metabolomics Facility and the Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, VIC, 3800, Australia.
  • Schmoll D; Biomedical Proteomics and Metabolomics Facility and the Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, VIC, 3800, Australia.
  • Kiens B; Institute for Biochemistry, Centre for Human and Molecular Biology (ZHMB), Saarland University, 66123, Saarbrücken, Germany.
  • Piper MDW; Sanofi-Aventis Deutschland GmbH, Industriepark Hoechst, Frankfurt am Main, 65926, Germany.
  • Heikenwälder M; Section of Molecular Physiology, Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, 2100, Copenhagen, Denmark.
  • Simpson SJ; School of Biological Sciences, School of Life and Environmental Sciences, Monash University, Clayton, VIC, 3800, Australia.
  • Bröer S; Division of Chronic Inflammation and Cancer, German Cancer Research Center, 69120, Heidelberg, Germany.
  • Andrikopoulos S; Charles Perkins Centre, School of Life and Environmental Sciences, University of Sydney, Sydney, NSW, Australia.
  • Müller OJ; Research School of Biology, Australian National University, Canberra, ACT, 0200, Australia.
  • Rose AJ; Department of Medicine (Austin Health), University of Melbourne, Heidelberg, VIC, 3084, Australia.
Nat Commun ; 11(1): 2894, 2020 06 09.
Article in En | MEDLINE | ID: mdl-32518324
ABSTRACT
Dietary protein dilution (DPD) promotes metabolic-remodelling and -health but the precise nutritional components driving this response remain elusive. Here, by mimicking amino acid (AA) supply from a casein-based diet, we demonstrate that restriction of dietary essential AA (EAA), but not non-EAA, drives the systemic metabolic response to total AA deprivation; independent from dietary carbohydrate supply. Furthermore, systemic deprivation of threonine and tryptophan, independent of total AA supply, are both adequate and necessary to confer the systemic metabolic response to both diet, and genetic AA-transport loss, driven AA restriction. Dietary threonine restriction (DTR) retards the development of obesity-associated metabolic dysfunction. Liver-derived fibroblast growth factor 21 is required for the metabolic remodelling with DTR. Strikingly, hepatocyte-selective establishment of threonine biosynthetic capacity reverses the systemic metabolic response to DTR. Taken together, our studies of mice demonstrate that the restriction of EAA are sufficient and necessary to confer the systemic metabolic effects of DPD.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Proteinuria / Amino Acids, Essential / Animal Feed Limits: Animals Language: En Journal: Nat Commun Journal subject: BIOLOGIA / CIENCIA Year: 2020 Document type: Article Affiliation country: Australia
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Proteinuria / Amino Acids, Essential / Animal Feed Limits: Animals Language: En Journal: Nat Commun Journal subject: BIOLOGIA / CIENCIA Year: 2020 Document type: Article Affiliation country: Australia