Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/23509
Title: Restriction of essential amino acids dictates the systemic metabolic response to dietary protein dilution.
Austin Authors: 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: Monash Institute of Pharmaceutical Sciences, Monash University, Melbourne, VIC, 3052, Australia
Department of Biochemistry and Molecular Biology, Metabolism, Diabetes and Obesity Program, Biomedicine Discovery Institute, Monash University, Clayton, VIC, 3800, Australia
Biomedical Proteomics and Metabolomics Facility and the Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, VIC, 3800, Australia
Charles Perkins Centre, School of Life and Environmental Sciences, University of Sydney, Sydney, NSW, Australia
Division of Chronic Inflammation and Cancer, German Cancer Research Center, 69120, Heidelberg, Germany
Sanofi-Aventis Deutschland GmbH, Industriepark Hoechst, Frankfurt am Main, 65926, Germany
Institute for Biochemistry, Centre for Human and Molecular Biology (ZHMB), Saarland University, 66123, Saarbrücken, Germany
School of Biological Sciences, School of Life and Environmental Sciences, Monash University, Clayton, VIC, 3800, Australia
Department of Medicine, Austin Health, The University of Melbourne, Heidelberg, Victoria, Australia
Research School of Biology, Australian National University, Canberra, ACT, 0200, Australia
German Center for Cardiovascular Research (DZHK), Partner sites Kiel and Heidelberg, Germany
Department of Internal Medicine III, University of Kiel, Kiel, Germany
Department of Internal Medicine III, University Hospital Heidelberg, Heidelberg, Germany
Section of Molecular Physiology, Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, 2100, Copenhagen, Denmark..
Issue Date: 9-Jun-2020
Date: 2020-06-09
Publication information: Nature Communications 2020; 11(1): 2894
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.
URI: https://ahro.austin.org.au/austinjspui/handle/1/23509
DOI: 10.1038/s41467-020-16568-z
ORCID: 0000-0001-7210-1976
0000-0003-0608-958X
0000-0002-4575-1233
0000-0001-8738-1878
0000-0001-9393-1071
0000-0001-5705-5625
0000-0003-0256-7687
0000-0002-8040-1634
0000-0001-8223-2638
0000-0001-9132-8244
Journal: Nature Communications
PubMed URL: 32518324
Type: Journal Article
Appears in Collections:Journal articles

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