Journal article

Restriction of essential amino acids dictates the systemic metabolic response to dietary protein dilution

Yann W Yap, Patricia M Rusu, Andrea Y Chan, Barbara C Fam, Andreas Jungmann, Samantha M Solon-Biet, Christopher K Barlow, Darren J Creek, Cheng Huang, Ralf B Schittenhelm, Bruce Morgan, Dieter Schmoll, Bente Kiens, Matthew DW Piper, Mathias Heikenwaelder, Stephen J Simpson, Stefan Broer, Sofianos Andrikopoulos, Oliver J Mueller, Adam J Rose



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 develo..

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Funding Acknowledgements

The authors wish to thank former lab members Thomas Gantert and Adriano Maida (German Cancer Research Center, Heidelberg, Germany) who conducted the pilot experiments for this study series. The experimental and technical assistance of Robert Lee (Monash Metabolic Phenotyping Facility, Australia), Anja Pfenninger (Sanofi-Aventis, Germany), Annika Zota, Max Schuster, and Sarah Lerch (German Cancer Research Center, Germany) is gratefully acknowledged. These studies were supported by Monash Biomedicine Discovery Institute laboratory start-up funds to A.J.R. as well as a Monash Joint Science-Medicine Interdisciplinary Research Seed Funding to A.J.R. and M.D.W.P.