Journal
MOLECULAR METABOLISM
Volume 2, Issue 1, Pages 31-37Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.molmet.2012.08.007
Keywords
FGF21; Adipose tissue; FGFR1; FGF19
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Funding
- Eli Lilly
- Susan Komen Foundation
- John S. Dunn Foundation
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FGF21 is a multifunctional metabolic regulator. The co-factor beta 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 (FR1K0) leads to a complete ablation of FGF21 stimulated transcriptional activity in this tissue. Furthermore, FR1K0 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 FR1K0 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. (C) 2012 Elsevier GmbH.
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