Fibroblast growth factor-19 action in the brain reduces food intake and body weight and improves glucose tolerance in male rats

Endocrinology. 2013 Jan;154(1):9-15. doi: 10.1210/en.2012-1891. Epub 2012 Nov 26.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Body Weight / drug effects*
  • Brain / drug effects*
  • Brain / metabolism*
  • Eating / drug effects*
  • Energy Metabolism / drug effects
  • Fibroblast Growth Factors / pharmacology*
  • Glucose / metabolism*
  • Humans
  • Male
  • Rats
  • Rats, Long-Evans


  • Fibroblast Growth Factors
  • Glucose