title: Fibroblast growth factor-19 action in the brain reduces food intake and body weight and improves glucose tolerance in male rats.
abstract: 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.
authors.affiliation: The University of Cincinnati College of Medicine, Department of Internal Medicine, Division of Endocrinology, Diabetes and Metabolism, Cincinnati, OH 45237, USA. karen.ryan@uc.edu
authors.forename: Karen K
authors.initials: KK
authors.lastname: Ryan
authors.forename: Rohit
authors.initials: R
authors.lastname: Kohli
authors.forename: Ruth
authors.initials: R
authors.lastname: Gutierrez-Aguilar
authors.forename: Shrawan G
authors.initials: SG
authors.lastname: Gaitonde
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Woods
authors.forename: Randy J
authors.initials: RJ
authors.lastname: Seeley
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D004435:Eating / Q000187:drug effects*; D004734:Energy Metabolism / Q000187:drug effects; D005346:Fibroblast Growth Factors / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D008297:Male; D051381:Rats; D020318:Rats, Long-Evans
chemical_list: D005346:Fibroblast Growth Factors; D005947:Glucose