Restriction of essential amino acids dictates the systemic metabolic response to dietary protein dilution.
Amino Acids, Essential
/ deficiency
Animal Feed
Animals
Dietary Proteins
/ metabolism
Female
Fibroblast Growth Factors
/ metabolism
Gastrointestinal Hormones
/ metabolism
Hepatocytes
/ metabolism
Homeostasis
Liver
/ metabolism
Male
Metabolome
Mice
Mice, Inbred C57BL
Obesity
/ metabolism
Phenotype
Proteinuria
/ metabolism
Threonine
/ deficiency
Tryptophan
/ deficiency
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
09 06 2020
09 06 2020
Historique:
received:
24
10
2019
accepted:
12
05
2020
entrez:
11
6
2020
pubmed:
11
6
2020
medline:
28
8
2020
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 32518324
doi: 10.1038/s41467-020-16568-z
pii: 10.1038/s41467-020-16568-z
pmc: PMC7283339
doi:
Substances chimiques
Amino Acids, Essential
0
Dietary Proteins
0
Gastrointestinal Hormones
0
fibroblast growth factor 21
0
Threonine
2ZD004190S
Fibroblast Growth Factors
62031-54-3
Tryptophan
8DUH1N11BX
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2894Références
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