Fibroblast Growth Factor-19 Action in the Brain Reduces Food Intake and Body Weight and Improves Glucose Tolerance in Male Rats
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Fibroblast growth factor-19 (FGF19) and its rodent ortholog, FGF15, are hormones produced in the distal small intestine and secreted into the circulation after a meal. In addition to controlling the enterohepatic circulation of bile acids, FGF15/19 also regulates systemic lipid and glucose metabolism. In these experiments we investigated the hypothesis that, like other gut-derived postprandial hormones, FGF15/19 can act in the central nervous system to elicit its metabolic effects. We found that FGF-receptors 1 and 4 are present in rat hypothalamus, and that their expression was reduced by up to 60% in high-fat fed rats relative to lean controls. Consistent with a potential role for brain FGF15/19 signaling to regulate energy and glucose homeostasis, and with a previous report that intracerebroventricular (i.c.v.) administration of FGF19 increases energy expenditure, we report that acute i.c.v. FGF19 reduces 24-h food intake and body weight, and acutely improves glucose tolerance. Conversely, i.c.v. administration of an FGF-receptor inhibitor increases food intake and impairs glucose tolerance, suggesting a physiological role for brain FGF receptor signaling. Together, these findings identify the central nervous system as a potentially important target for the beneficial effects of FGF19 in the treatment of obesity and diabetes.
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Fgf15 can signal through the brain to modulate glucose homeostasis and glucagon secretion.
“Importantly, Fgf15 can also signal through the brain to modulate glucose homeostasis 45 and glucagon secretion 46.”
From Inter‐organ communication: a gatekeeper for metabolic health (2019) · cites this paper as [45]
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- Authors
- Ryan, K. K., Kohli, R., Gutierrez-Aguilar, R., Gaitonde, S. G., Woods, S. C., & Seeley, R. J.
- Affiliations
- University of Cincinnati (US)
- Cincinnati Children's Hospital Medical Center (US)
- The University of Cincinnati College of Medicine, Department of Internal Medicine, Division of Endocrinology, Diabetes and Metabolism (K.K.R., R.G.-A., R.J.S.), Cincinnati, Ohio 45237
- Department of Surgery (S.G.G.), Cincinnati, Ohio 45237
- Department of Psychiatry and Behavioral Neuroscience (S.C.W.), Cincinnati, Ohio 45237
- Corresponding author
- Ryan, Karen K.
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 2013-01-01
- Volume
- 154
- Issue
- 1
- Pages
- 9-15
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- PMC
- PMC3529386
- OpenAlex
- W1976348644
- Cited by
- 185
- References
- 34
- Citations by year
- 2026: 10 · 2025: 8 · 2024: 14 · 2023: 13 · 2022: 18 · 2021: 22 · 2020: 13 · 2019: 16 · 2018: 16 · 2017: 12 · 2016: 8 · 2015: 18 · 2014: 4 · 2013: 13
- FWCI
- 4.50
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Endocrinology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Eli Lilly and Company
- Pfizer
- University of Cincinnati
- Zafgen
- Novo Nordisk
- National Institutes of Health (UL1TR000077, DK017844, HL111319)
- National Heart, Lung, and Blood Institute (HL111319, R00HL111319, K99HL111319)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK084310, DK 017844, F32DK082173, K08DK084310, DK-0938+48, R01DK017844, R01DK093848, R37DK017844, DK082173)
- National Center for Advancing Translational Sciences
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fibroblast Growth Factor Research
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Keywords
- FGF19, FGF15, fibroblast growth factor receptor, hypothalamus, dietary intake, body weight, glucose tolerance, central nervous system, gastrointestinal hormones, energy homeostasis, obesity, diabetes mellitus, high-fat diet, energy expenditure
- MeSH terms
- Animals, Body Weight, Brain, Eating, Energy Metabolism, Fibroblast Growth Factors, Glucose, Humans, Male, Rats, Long-Evans, Rats
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