Cited by 215Fibroblast Growth Factor ResearchAdipose Tissue and MetabolismPeroxisome Proliferator-Activated Receptors

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Central Fibroblast Growth Factor 21 Browns White Fat via Sympathetic Action in Male Mice

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Douris, Nicholas, Stevanovic, Darko M., Fisher, ffolliott M., Cisu, Theodore I., Chee, Melissa J., Nguyen, Ngoc L., Zarebidaki, Eleen, Adams, Andrew C., Kharitonenkov, Alexei, Flier, Jeffrey S., Bartness, Timothy J., Maratos-Flier, Eleftheria·2015·Endocrinology

DOI 10.1210/en.2014-2001PMC PMC4475718

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Abstract

Fibroblast growth factor 21 (FGF21) has multiple metabolic actions, including the induction of browning in white adipose tissue. Although FGF21 stimulated browning results from a direct interaction between FGF21 and the adipocyte, browning is typically associated with activation of the sympathetic nervous system through cold exposure. We tested the hypothesis that FGF21 can act via the brain, to increase sympathetic activity and induce browning, independent of cell-autonomous actions. We administered FGF21 into the central nervous system via lateral ventricle infusion into male mice and found that the central treatment increased norepinephrine turnover in target tissues that include the inguinal white adipose tissue and brown adipose tissue. Central FGF21 stimulated browning as assessed by histology, expression of uncoupling protein 1, and the induction of gene expression associated with browning. These effects were markedly attenuated when mice were treated with a β-blocker. Additionally, neither centrally nor peripherally administered FGF21 initiated browning in mice lacking β-adrenoceptors, demonstrating that an intact adrenergic system is necessary for FGF21 action. These data indicate that FGF21 can signal in the brain to activate the sympathetic nervous system and induce adipose tissue thermogenesis.

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Authors: Douris, N., Stevanovic, D. M., Fisher, F. M., Cisu, T. I., Chee, M. J., Nguyen, N. L., Zarebidaki, E., Adams, A. C., Kharitonenkov, A., Flier, J. S., Bartness, T. J., & Maratos-Flier, E.
Affiliations: Beth Israel Deaconess Medical Center (US)
Division of Endocrinology (N.D., D.M.S., f.M.F., T.I.C., M.J.C., J.S.F., E.M.-F.), Beth Israel Deaconess Medical Center, Department of Medicine, Harvard Medical School, Boston, Massachusetts 02215-5491
Georgia State University (US)
Eli Lilly (United States) (US)
ORCID: Douris, Nicholas
Cisu, Theodore I.
Chee, Melissa J.
Zarebidaki, Eleen
Adams, Andrew C.
Kharitonenkov, Alexei
Flier, Jeffrey S.
Bartness, Timothy J.
Venue: Endocrinology
Publisher: The Endocrine Society
Published: 2015-04-29
Volume: 156
Issue: 7
Pages: 2470-2481
ISSN: 0013-7227 (ISSN-L)
1945-7170
DOI: 10.1210/en.2014-2001
PMC: PMC4475718
OpenAlex: W1983477298
Cited by: 215
References: 73
Citations by year: 2026: 11 · 2025: 10 · 2024: 11 · 2023: 14 · 2022: 19 · 2021: 16 · 2020: 23 · 2019: 30 · 2018: 25 · 2017: 22 · 2016: 24 · 2015: 10
FWCI: 11.72
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Endocrinology (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Institute of Diabetes and Digestive and Kidney Diseases (R37DK35254, R01DK078358, 5T32DK751627, R01DK028082, R37DK035254, R01DK035254)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fibroblast Growth Factor Research
Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
Keywords: FGF21, white adipose tissue browning, brown adipose tissue, sympathetic nervous system, central nervous system, norepinephrine turnover, UCP1, thermogenesis, beta-adrenergic receptors, beta-blockers, brain signaling, adipose tissue
MeSH terms: Uncoupling Protein 1, Adrenergic beta-Antagonists, Animals, Adipose Tissue, Brown, Fibroblast Growth Factors, Ion Channels, Male, Receptors, Adrenergic, beta, Sympathetic Nervous System, Receptors, Adrenergic, beta-1, Receptors, Adrenergic, beta-2, Mice, Knockout, Receptors, Adrenergic, beta-3, Thermogenesis, Mitochondrial Proteins, Mice, Adipose Tissue, White, Adipocytes, Brown, Adipocytes, White, Infusions, Intraventricular

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Central Fibroblast Growth Factor 21 Browns White Fat via Sympathetic Action in Male Mice

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