Elsevier

Molecular Metabolism

Volume 2, Issue 1, February 2013, Pages 31-37
Molecular Metabolism

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

https://doi.org/10.1016/j.molmet.2012.08.007Get rights and content
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open access

Abstract

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 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.

Abbreviations

BAT
Brown adipose tissue
βHB
β-HydroxyButyrate
KLB
βKlotho
DIO
Diet induced obese
EGR1
Early growth response protein 1
FGF19
Fibroblast growth factor 19
FGF21
Fibroblast growth factor 21
FGFR
Fibroblast growth factor receptor
FFA
Free fatty acids
ACADL
Long chain acetyl-CoA dehydrogenase
PGC1α
PPARγ coactivator 1α
SCD1
Stearoyl-Coenzyme A desaturase 1
TG
Triglycerides
WAT
White adipose tissue
UCP1
Uncoupling protein 1
ACADVL
Very long chain acetyl-CoA dehydrogenase.

Keywords

FGF21
Adipose tissue
FGFR1
FGF19

Cited by (0)

A.C.A. and C.Y. contributed equally to this work.