The Role of FGF19 and MALRD1 in Enterohepatic Bile Acid Signaling

Front Endocrinol (Lausanne). 2022 Jan 18:12:799648. doi: 10.3389/fendo.2021.799648. eCollection 2021.

Abstract

Bile acids are the catabolic end products of cholesterol metabolism that are best known for their role in the digestion of lipids. In the last two decades, extensive investigation has shown bile acids to be important signaling molecules in metabolic processes throughout the body. Bile acids are ligands that can bind to several receptors, including the nuclear receptor farnesoid X receptor (FXR) in ileal enterocytes. FXR activation induces the expression of fibroblast growth factor (FGF) 15/19, a hormone that can modulate bile acid levels, repress gluconeogenesis and lipogenesis, and promote glycogen synthesis. Recent studies have described a novel intestinal protein, MAM and LDL Receptor Class A Domain containing 1 (MALRD1) that positively affects FGF15/19 levels. This signaling pathway presents an exciting target for treating metabolic disease and bile acid-related disorders.

Keywords: FGF19; MALRD1; bile acid signaling; glucose metabolism; lipid metabolism.

Publication types

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

MeSH terms

  • Animals
  • Bile Acids and Salts / metabolism*
  • Enterohepatic Circulation
  • Fibroblast Growth Factors / metabolism*
  • Humans
  • Intestine, Small / metabolism*
  • Liver / metabolism*
  • Receptors, LDL / metabolism*
  • Signal Transduction

Substances

  • Bile Acids and Salts
  • FGF19 protein, human
  • MALRD1 protein, human
  • Receptors, LDL
  • Fibroblast Growth Factors