Bridging cell surface receptor with nuclear receptors in control of bile acid homeostasis

Acta Pharmacol Sin. 2015 Jan;36(1):113-8. doi: 10.1038/aps.2014.118. Epub 2014 Dec 15.

Abstract

Bile acids (BAs) are traditionally considered as "physiological detergents" for emulsifying hydrophobic lipids and vitamins due to their amphipathic nature. But accumulating clinical and experimental evidence shows an association between disrupted BA homeostasis and various liver disease conditions including hepatitis infection, diabetes and cancer. Consequently, BA homeostasis regulation has become a field of heavy interest and investigation. After identification of the Farnesoid X Receptor (FXR) as an endogenous receptor for BAs, several nuclear receptors (SHP, HNF4α, and LRH-1) were also found to be important in regulation of BA homeostasis. Some post-translational modifications of these nuclear receptors have been demonstrated, but their physiological significance is still elusive. Gut secrets FGF15/19 that can activate hepatic FGFR4 and its downstream signaling cascade, leading to repressed hepatic BA biosynthesis. However, the link between the activated kinases and these nuclear receptors is not fully elucidated. Here, we review the recent literature on signal crosstalk in BA homeostasis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Bile Acids and Salts / metabolism*
  • Homeostasis / physiology*
  • Humans
  • Receptors, Cell Surface / metabolism*
  • Receptors, Cytoplasmic and Nuclear / metabolism*
  • Signal Transduction / physiology

Substances

  • Bile Acids and Salts
  • Receptors, Cell Surface
  • Receptors, Cytoplasmic and Nuclear