FGF21 acts centrally to induce sympathetic nerve activity, energy expenditure, and weight loss

Bryn M. Owen, Xunshan Ding, Donald A. Morgan, Katie Colbert Coate, Angie L. Bookout, Kamal Rahmouni, Steven A. Kliewer, David J. Mangelsdorf

Research output: Contribution to journalArticle

192 Citations (Scopus)

Abstract

The mechanism by which pharmacologic administration of the hormone FGF21 increases energy expenditure to cause weight loss in obese animals is unknown. Here we report that FGF21 acts centrally to exert its effects on energy expenditure and body weight in obese mice. Using tissue-specific knockout mice, we show that βKlotho, the obligate coreceptor for FGF21, is required in the nervous system for these effects. FGF21 stimulates sympathetic nerve activity to brown adipose tissue through a mechanism that depends on the neuropeptide corticotropin-releasing factor. Our findings provide an unexpected mechanistic explanation for the strong pharmacologic effects of FGF21 on energy expenditure and weight loss in obese animals.

Original languageEnglish (US)
Pages (from-to)670-677
Number of pages8
JournalCell Metabolism
Volume20
Issue number4
DOIs
StatePublished - Oct 7 2014

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Energy Metabolism
Weight Loss
Obese Mice
Brown Adipose Tissue
Corticotropin-Releasing Hormone
Neuropeptides
Knockout Mice
Nervous System
Body Weight
fibroblast growth factor 21
Hormones

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Physiology

Cite this

FGF21 acts centrally to induce sympathetic nerve activity, energy expenditure, and weight loss. / Owen, Bryn M.; Ding, Xunshan; Morgan, Donald A.; Coate, Katie Colbert; Bookout, Angie L.; Rahmouni, Kamal; Kliewer, Steven A.; Mangelsdorf, David J.

In: Cell Metabolism, Vol. 20, No. 4, 07.10.2014, p. 670-677.

Research output: Contribution to journalArticle

Owen, Bryn M. ; Ding, Xunshan ; Morgan, Donald A. ; Coate, Katie Colbert ; Bookout, Angie L. ; Rahmouni, Kamal ; Kliewer, Steven A. ; Mangelsdorf, David J. / FGF21 acts centrally to induce sympathetic nerve activity, energy expenditure, and weight loss. In: Cell Metabolism. 2014 ; Vol. 20, No. 4. pp. 670-677.
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