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

doi:10.1016/j.cmet.2014.07.012

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

Journal article

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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 and David J Mangelsdorf

Cell metabolism, Vol.20(4), pp.670-677

10/07/2014

DOI: 10.1016/j.cmet.2014.07.012

PMCID: PMC4192037

PMID: 25130400

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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.

Thermogenesis - genetics

Membrane Proteins - genetics

Sympathetic Nervous System - drug effects

Mice, Inbred C57BL

Fibroblast Growth Factors - genetics

Mice, Transgenic

Fibroblast Growth Factors - pharmacology

Weight Loss - drug effects

RNA, Messenger - metabolism

Sympathetic Nervous System - metabolism

Corticotropin-Releasing Hormone - metabolism

Mice, Knockout

Fibroblast Growth Factors - metabolism

Membrane Proteins - deficiency

Animals

Hypothalamus - metabolism

Mice, Obese

Adipose Tissue, Brown - metabolism

Corticotropin-Releasing Hormone - genetics

Mice

Energy Metabolism - drug effects

Details

Title: Subtitle: FGF21 acts centrally to induce sympathetic nerve activity, energy expenditure, and weight loss
Creators: Bryn M Owen - Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
Xunshan Ding - Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
Donald A Morgan - Department of Pharmacology, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA
Katie Colbert Coate - Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
Angie L Bookout - Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
Kamal Rahmouni - Department of Pharmacology, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA
Steven A Kliewer - Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Electronic address: steven.kliewer@utsouthwestern.edu
David J Mangelsdorf - Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Electronic address: davo.mango@utsouthwestern.edu
Resource Type: Journal article
Publication Details: Cell metabolism, Vol.20(4), pp.670-677
Publisher: United States
DOI: 10.1016/j.cmet.2014.07.012
PMID: 25130400
PMCID: PMC4192037
ISSN: 1550-4131
eISSN: 1932-7420
Grant note: R01DK067158 / NIDDK NIH HHS R01 DK067158 / NIDDK NIH HHS HL084207 / NHLBI NIH HHS Howard Hughes Medical Institute GM007062 / NIGMS NIH HHS 1F32DK098908 / NIDDK NIH HHS P01 HL084207 / NHLBI NIH HHS T32 GM007062 / NIGMS NIH HHS F32 DK098908 / NIDDK NIH HHS
Language: English
Date published: 10/07/2014
Academic Unit: Iowa Neuroscience Institute; Neuroscience and Pharmacology; Internal Medicine
Record Identifier: 9984040264902771

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