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Fibroblast growth factor 21 is not required for the antidiabetic actions of the thiazoladinediones

Andrew C Adams1, Tamer Coskun, Christine C Cheng

  • 1Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, IN 46285, USA.

Molecular Metabolism
|September 20, 2013
PubMed

Insights

Fibroblast growth factor 21 (FGF21) is not essential for rosiglitazone

Area of Science:

  • Metabolic regulation
  • Endocrinology
  • Pharmacology

Background:

  • Fibroblast growth factor 21 (FGF21) is an emerging metabolic regulator.
  • FGF21 was previously proposed as a fed-state inducible factor in adipose tissue, potentially mediating PPARγ-driven effects.
  • Mice lacking FGF21 were suggested to be refractory to rosiglitazone treatment.

Purpose of the Study:

  • To investigate the role of FGF21 in PPARγ-driven pharmacology.
  • To determine if FGF21 is necessary for rosiglitazone's metabolic effects and side effects.

Main Methods:

  • Experiments were conducted in control and FGF21 knockout (FGF21KO) mice.
  • Rosiglitazone efficacy was assessed across various metabolic endpoints.
  • Transcriptional signatures and cytokine secretion profiles were analyzed.

Main Results:

  • Rosiglitazone was equally efficacious in control and FGF21KO mice.
  • Enhanced glycemic control, improved lipid homeostasis, and adipose accumulation occurred in both genotypes.
  • The transcriptional and cytokine profiles of rosiglitazone action were preserved in FGF21KO animals.
  • FGF21 expression in adipose tissue was comparable in fasted and fed states.

Conclusions:

  • FGF21 is not necessary for the metabolic events downstream of PPARγ activation by rosiglitazone.
  • This study presents a new perspective on the FGF21/PPARγ interplay.
  • FGF21's role in mediating PPARγ pharmacology may be less critical than previously thought.
Keywords:
AdiponectinFGF21MetabolismPPARγRosiglitazone

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