Fibroblast Growth Factor-19 Action in the Brain Reduces Food Intake and Body Weight and Improves Glucose Tolerance in Male Rats

• Published in: Endocrinology (Philadelphia) Vol. 154; no. 1; pp. 9 - 15
• Main Authors: Ryan, Karen K, Kohli, Rohit, Gutierrez-Aguilar, Ruth, Gaitonde, Shrawan G, Woods, Stephen C, Seeley, Randy J
• Format: Journal Article
• Language: English
• Published: Chevy Chase, MD Endocrine Society 01-01-2013; Oxford University Press
• Subjects: Animals; Bile acids; Biological and medical sciences; Body weight; Body Weight - drug effects; Brain; Brain - drug effects; Brain - metabolism; Brief Report; Central nervous system; Diabetes mellitus; Eating - drug effects; Energy expenditure; Energy Metabolism - drug effects; Fibroblast growth factors; Fibroblast Growth Factors - pharmacology; Fibroblasts; Food conversion; Food intake; Fundamental and applied biological sciences. Psychology; Glucose; Glucose - metabolism; Glucose tolerance; Growth factors; Homeostasis; Hormones; Humans; Hypothalamus; Intestine; Lipid metabolism; Lipids; Male; Nervous system; Physiological effects; Rats; Rats, Long-Evans; Receptors; Small intestine; Vertebrates: endocrinology; Fibroblast growth factor; Rat; Body weight; Rodentia; Central nervous system; Tolerance; Male; Glucose; Feeding; Encephalon; Vertebrata; Mammalia; Food intake; Animal
• ISSN: 0013-7227; 1945-7170
• DOI: 10.1210/en.2012-1891

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.