Dataset Information

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

ABSTRACT: Dietary protein dilution (DPD) promotes metabolic remodelling and health but the precise nutritional components driving this response remain elusive. Here we demonstrate that dietary amino acids (AA) are sufficient and necessary to drive the response to DPD. In particular, the restriction of dietary essential AA (EAA) supply, but not non-EAA, drives the systemic metabolic response to total AA deprivation. Furthermore, systemic deprivation of Thr and Trp, 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. Thr is also potentially limiting in low-protein diet fed humans, and dietary Thr restriction (DTR) retarded the development of obesity-associated metabolic dysfunction in mice. Liver-derived fibroblast growth factor 21 was required for the metabolic remodelling with DTR. Strikingly, hepatocyte-selective establishment of Thr biosynthetic capacity reversed the systemic response to DTR. Taken together, our studies demonstrate that the restriction of EAA are sufficient and necessary to confer the systemic metabolic effects of DPD.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Liver

SUBMITTER: Cheng Huang

LAB HEAD: Adam Rose

PROVIDER: PXD018205 | Pride | 2020-06-15

REPOSITORIES: Pride

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

Yap Yann W YW Rusu Patricia M PM Chan Andrea Y AY Fam Barbara C BC Jungmann Andreas A Solon-Biet Samantha M SM Barlow Christopher K CK Creek Darren J DJ Huang Cheng C Schittenhelm Ralf B RB Morgan Bruce B Schmoll Dieter D Kiens Bente B Piper Matthew D W MDW Heikenwälder Mathias M Simpson Stephen J SJ Bröer Stefan S Andrikopoulos Sofianos S Müller Oliver J OJ Rose Adam J AJ

Nature communications 20200609 1

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 supp ...[more]

PMID: 32518324

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