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Central Fibroblast Growth Factor 21 Browns White Fat via Sympathetic Action in Male Mice
Open accessAbstract
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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“FGF21 administration increases sympathetic nerve activity to BAT (101) and WAT (28), and browning of WAT depots (28, 101).”
From Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis (2018) · cites this paper as [28]
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Metadata
- 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
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 2015-04-29
- Volume
- 156
- Issue
- 7
- Pages
- 2470-2481
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- 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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