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The breadth of FGF21's metabolic actions are governed by FGFR1 in adipose tissue.


ABSTRACT: FGF21 is a multifunctional metabolic regulator. The co-factor ?Klotho (KLB) allows FGF21 to signal via FGF receptors. Given the widespread nature of FGFR expression and KLB presence in several organs, it remains unclear which tissue/FGFR isoform determine FGF21 action. Here we show that deletion of FGFR1 in fat (FR1KO) leads to a complete ablation of FGF21 stimulated transcriptional activity in this tissue. Furthermore, FR1KO mice showed no FGF21-mediated lowering of plasma glucose, insulin and triglycerides, altered serum levels of adipokines, no increase in energy expenditure, but preserved reductions in serum/liver FFAs as compared to wild type mice. Of importance, the anti-glycaemic actions of FGF19 were fully evident in FR1KO mice implying that FGF19 functions in a FGFR1/adipose independent manner. Taken together, our findings reveal the existence of an adipose FGFR1 driven axis of cross-tissue communication which defines several aspects of FGF21 biology and delineates mechanistic distinctions between FGF21 and FGF19.

SUBMITTER: Adams AC 

PROVIDER: S-EPMC3757657 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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The breadth of FGF21's metabolic actions are governed by FGFR1 in adipose tissue.

Adams Andrew C AC   Yang Chaofeng C   Coskun Tamer T   Cheng Christine C CC   Gimeno Ruth E RE   Luo Yongde Y   Kharitonenkov Alexei A  

Molecular metabolism 20120828 1


FGF21 is a multifunctional metabolic regulator. The co-factor βKlotho (KLB) allows FGF21 to signal via FGF receptors. Given the widespread nature of FGFR expression and KLB presence in several organs, it remains unclear which tissue/FGFR isoform determine FGF21 action. Here we show that deletion of FGFR1 in fat (FR1KO) leads to a complete ablation of FGF21 stimulated transcriptional activity in this tissue. Furthermore, FR1KO mice showed no FGF21-mediated lowering of plasma glucose, insulin and  ...[more]

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