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Publication
FGF21 Mediates the Thermogenic and Insulin-Sensitizing Effects of Dietary
Methionine Restriction but Not Its Effects on Hepatic Lipid Metabolism.
Authors Wanders D, Forney LA, Stone KP, Burk DH, Pierse A, Gettys TW
Submitted By Submitted Externally on 11/9/2017
Status Published
Journal Diabetes
Year 2017
Date Published 4/1/2017
Volume : Pages 66 : 858 - 867
PubMed Reference 28096260
Abstract Dietary methionine restriction (MR) produces a rapid and persistent remodeling
of white adipose tissue (WAT), an increase in energy expenditure (EE), and
enhancement of insulin sensitivity. Recent work established that hepatic
expression of FGF21 is robustly increased by MR. Fgf21(-/-) mice were used to
test whether FGF21 is an essential mediator of the physiological effects of
dietary MR. The MR-induced increase in energy intake and EE and activation of
thermogenesis in WAT and brown adipose tissue were lost in Fgf21(-/-) mice.
However, dietary MR produced a comparable reduction in body weight and adiposity
in both genotypes because of a negative effect of MR on energy intake in
Fgf21(-/-) mice. Despite the similar loss in weight, dietary MR produced a more
significant increase in in vivo insulin sensitivity in wild-type than in
Fgf21(-/-) mice, particularly in heart and inguinal WAT. In contrast, the
ability of MR to regulate lipogenic and integrated stress response genes in
liver was not compromised in Fgf21(-/-) mice. Collectively, these findings
illustrate that FGF21 is a critical mediator of the effects of dietary MR on EE,
remodeling of WAT, and increased insulin sensitivity but not of its effects on
hepatic gene expression.




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