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

Andrew C. Adams, Chaofeng Yang, Tamer Coskun, Christine C. Cheng, Ruth E. Gimeno, Yongde Luo, Alexei Kharitonenkov

Research output: Contribution to journalArticle

157 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)31-37
Number of pages7
JournalMolecular Metabolism
Volume2
Issue number1
DOIs
StatePublished - Feb 2013

    Fingerprint

Keywords

  • Adipose tissue
  • FGF19
  • FGF21
  • FGFR1

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Adams, A. C., Yang, C., Coskun, T., Cheng, C. C., Gimeno, R. E., Luo, Y., & Kharitonenkov, A. (2013). The breadth of FGF21's metabolic actions are governed by FGFR1 in adipose tissue. Molecular Metabolism, 2(1), 31-37. https://doi.org/10.1016/j.molmet.2012.08.007