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Dietary Methionine Restriction Signals to the Brain Through Fibroblast Growth Factor 21 to Regulate Energy Balance and Remodeling of Adipose Tissue
Author(s) -
Forney Laura A.,
Fang Han,
Sims Landon C.,
Stone Kirsten P.,
Vincik Leighann Y.,
Vick Alicia M.,
Gibson Amanda N.,
Burk David H.,
Gettys Thomas W.
Publication year - 2020
Publication title -
obesity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.438
H-Index - 199
eISSN - 1930-739X
pISSN - 1930-7381
DOI - 10.1002/oby.22919
Subject(s) - fgf21 , adipose tissue , methionine , medicine , endocrinology , white adipose tissue , fibroblast growth factor , biology , brain tissue , gene expression , gene , biochemistry , receptor , amino acid
Objective Restricting dietary methionine to 0.17% in mice increases energy expenditure (EE), reduces fat deposition, and improves metabolic health by increasing hepatic fibroblast growth factor 21 (FGF21). The goal of this study was to compare each of these responses in mice with the coreceptor for FGF21 deleted in either adipose tissue or the brain. Methods Methionine‐restriction (MR) diets were fed to age‐matched cohorts of mice with the coreceptor for FGF21 deleted in either adipose tissue or the brain. The physiological and transcriptional responses to MR were compared in the respective cohorts. Results Tissue‐specific deletion of the FGF21 coreceptor in adipose tissue did not abrogate the ability of dietary MR to increase EE and reduce fat deposition. Tissue‐specific deletion of the FGF21 coreceptor from the brain produced mice that were unable to respond to the effects of MR on EE or the remodeling of adipose tissue. Conclusions The increase in FGF21 produced by dietary MR acts primarily in the brain to produce its physiological effects on energy balance. In contrast, the effects of MR on hepatic gene expression were intact in both models, supporting a mechanism that directly links detection of reduced methionine in the liver to transcriptional mechanisms that alter gene expression in the liver.