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

Nature Communications
Yann W YapAdam J Rose

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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Citations

Jan 7, 2021·Obesity Reviews : an Official Journal of the International Association for the Study of Obesity·Patrick C EvenDaniel Tomé
Oct 15, 2020·The Proceedings of the Nutrition Society·Daniel ToméDalila Azzout-Marniche
Jul 16, 2021·Translational Medicine of Aging·Reji Babygirija, Dudley W Lamming
Oct 12, 2021·Basic & Clinical Pharmacology & Toxicology·Amit JoharapurkarMukul Jain
Nov 18, 2021·Molecular Metabolism·Fei Xiao, Feifan Guo
Jan 16, 2022·BMC Biology·Samantha M Solon-BietAlistair M Senior

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