Role of Fibroblast Growth Factor 19 in Maintaining Nutrient Homeostasis and Disease

Abstract

Fibroblast growth factor 19 (FGF19) is a kind of gut-derived postprandial hormone. As an atypical member of the FGF family, FGF19 functions as an endocrine hormone except regulating cell growth and differentiation. FGF19 plays a key role in coordination of liver bile acid biosynthesis and gallbladder motility, and acts as a regulator of metabolic homeostasis, including strengthening insulin sensitivity, decreasing triglyceride concentration and reducing body weight. FGF19 is related with coronary artery disease and renal function. The multiple beneficial effects make FGF19 an attractive drug candidate for regulating bile acid homeostasis and treating metabolic disease. However, an important caveat is that FGF19 could stimulate proliferation which may be associated with cancer. Pharmacological study should focus on developing novel FGF19 analogues with potent metabolic effects but no proliferative effects of FGF19. This paper summarizes the recent advances in studies on FGF19. Fibroblast growth factors (FGFs) are a group of proteins involved in various biological processes, such as development, repair, and metabolism. Currently, the human FGF family consists of 22 members which can be divided into 7 subfamilies according to their gene locus and action modes, including the intracellular FGF11/12/13/14 subfamily, hormone-like (endocrine) FGF19/21/23 subfamily, and canonical FGF subfamily containing FGF1/2/5, FGF3/4/6, FGF7/10/22, FGF8/17/18, and FGF9/16/20. Most FGFs play an important role in regulating cell growth and differentiation, while FGF19 together with FGF21 and FGF23 has no or mild mitogenic effects. However, it functions via systemic, hormone-like effects. FGF19 (the human ortholog of murine FGF15) is primarily secreted in the small intestine but regulates bile acid synthesis in the liver both in rodents and in humans, and regulates glucose, lipid and energy homeostasis.