Mini-review: endocrine actions of fibroblast growth factor 19

Abstract

Fibroblast growth factor (FGF) 19 is an atypical member of the fibroblast growth factor family of signaling molecules. FGF19, FGF21, and FGF23 comprise a phylogenetic subfamily with attributes that distinguish them from typical FGFs. The FGF19 subfamily has reduced heparin binding resulting from a disrupted beta-trefoil domain. Reduced heparin binding allows these FGFs to diffuse beyond their site of origin and act as endocrine hormones. This family of FGFs is regulated, at least in part, by nuclear hormone receptors. FGF19 expression is regulated by the farnesoid X receptor, a nuclear hormone receptor that is a key regulator of bile acid biosynthesis and transport. In line with its regulation by a bile acid receptor, FGF19 is involved in the regulation of bile acid biosynthesis and gallbladder filling. FGF19 originates from intestine and signals to liver via the portal circulation with a pronounced diurnal pattern. FGF19 is the only FGF to not have a closely related mouse homologue. The mouse homologue of FGF19, called FGF15, is only 53% identical to the human FGF19. FGF19 transgenic mice and mice administered exogenous FGF19 are resistant to the effects of a high fat diet, suggesting FGF19 may play a role in metabolic signaling pathways. Hepatocellular carcinoma is seen in mice, predominantly female mice, exposed to FGF19. Further investigation into the cellular mechanisms involved in these activities will allow better understanding of FGF19 biology in the context of human physiology.