Endocrine Regulation of the Fasting Response by PPARα-Mediated Induction of Fibroblast Growth Factor 21

Takeshi Inagaki, Paul Dutchak, Guixiang Zhao, Xunshan Ding, Laurent Gautron, Vinay Parameswara, Yong Li, Regina Goetz, Moosa Mohammadi, Victoria Esser, Joel K Elmquist, Robert D. Gerard, Shawn C Burgess, Robert E Hammer, David J Mangelsdorf, Steven A Kliewer

Research output: Contribution to journalArticle

900 Scopus citations

Abstract

Peroxisome proliferator-activated receptor α (PPARα) regulates the utilization of fat as an energy source during starvation and is the molecular target for the fibrate dyslipidemia drugs. Here, we identify the endocrine hormone fibroblast growth factor 21 (FGF21) as a mediator of the pleiotropic actions of PPARα. FGF21 is induced directly by PPARα in liver in response to fasting and PPARα agonists. FGF21 in turn stimulates lipolysis in white adipose tissue and ketogenesis in liver. FGF21 also reduces physical activity and promotes torpor, a short-term hibernation-like state of regulated hypothermia that conserves energy. These findings demonstrate an unexpected role for the PPARα-FGF21 endocrine signaling pathway in regulating diverse metabolic and behavioral aspects of the adaptive response to starvation.

Original languageEnglish (US)
Pages (from-to)415-425
Number of pages11
JournalCell Metabolism
Volume5
Issue number6
DOIs
Publication statusPublished - Jun 6 2007

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Keywords

  • HUMDISEASE

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Physiology

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