Mechanisms of enterohepatic fibroblast growth factor 15/19 signaling in health and disease

Cytokine Growth Factor Rev. 2015 Dec;26(6):625-35. doi: 10.1016/j.cytogfr.2015.07.016. Epub 2015 Jul 28.

Abstract

The gut-derived hormone fibroblast growth factor 15/19 (FGF15/19) is an emerging versatile regulator of various metabolic pathways. As such, FGF15/19 has been implicated in homeostatic control of bile acid, carbohydrate and lipid metabolism in multiple target organs including the liver, adipose tissue and brain. In line with this, growing evidence suggests that dysregulation of FGF15/19 contributes to a number of metabolic and bile acid-associated disorders such as fatty liver disease, Type 2 diabetes and different gastrointestinal dysfunctions. In this review we summarize the current knowledge on the organ-specific functions of FGF15/19 and address their underlying molecular mechanisms. Moreover, recent advances in the characterization of factors that control the release of the hormone in the gut will be discussed and linked to the current view of how alterations of FGF15/19 signaling may contribute to disease development. Finally, the suitability of FGF15/19 as a potential therapeutic target will be critically reviewed.

Keywords: Bile acid signaling; Energy metabolism; Fibroblast growth factor 15/19; Liver disease; Nuclear receptors; Obesity.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adipose Tissue / metabolism
  • Animals
  • Bile Acids and Salts / metabolism
  • Brain / metabolism
  • Diabetes Mellitus, Type 2 / metabolism
  • Fibroblast Growth Factors / biosynthesis
  • Fibroblast Growth Factors / genetics
  • Fibroblast Growth Factors / metabolism*
  • Homeostasis
  • Humans
  • Lipid Metabolism
  • Liver / metabolism*
  • Mice
  • Obesity / metabolism
  • Signal Transduction

Substances

  • Bile Acids and Salts
  • FGF19 protein, human
  • fibroblast growth factor 15, mouse
  • Fibroblast Growth Factors