Deciphering the Nuclear Bile Acid Receptor FXR Paradigm

Nucl Recept Signal. 2010 Nov 19;8:e005. doi: 10.1621/nrs.08005.

Abstract

Originally called retinoid X receptor interacting protein 14 (RIP14), the farnesoid X receptor (FXR) was renamed after the ability of its rat form to bind supra-physiological concentrations of farnesol. In 1999 FXR was de-orphanized since primary bile acids were identified as natural ligands. Strongly expressed in the liver and intestine, FXR has been shown to be the master transcriptional regulator of several entero-hepatic metabolic pathways with relevance to the pathophysiology of conditions such as cholestasis, fatty liver disease, cholesterol gallstone disease, intestinal inflammation and tumors. Furthermore, given the importance of FXR in the gut-liver axis feedbacks regulating lipid and glucose homeostasis, FXR modulation appears to have great input in diseases such as metabolic syndrome and diabetes. Exciting results from several cellular and animal models have provided the impetus to develop synthetic FXR ligands as novel pharmacological agents. Fourteen years from its discovery, FXR has gone from bench to bedside; a novel nuclear receptor ligand is going into clinical use.

Publication types

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

MeSH terms

  • Animals
  • Atherosclerosis / drug therapy
  • Bile Acids and Salts / chemistry*
  • Bile Acids and Salts / genetics
  • Bile Acids and Salts / metabolism
  • Cholestasis / drug therapy
  • Cholestasis / metabolism
  • Diabetes Mellitus / drug therapy
  • Gallstones / drug therapy
  • Gallstones / metabolism
  • Gastrointestinal Stromal Tumors / drug therapy
  • Gastrointestinal Stromal Tumors / metabolism
  • Gene Expression Regulation / genetics
  • Glucose / metabolism
  • Hyperlipidemias / drug therapy
  • Intestinal Diseases / drug therapy
  • Intestinal Diseases / metabolism
  • Liver Neoplasms / drug therapy
  • Liver Neoplasms / metabolism
  • Liver Regeneration
  • Rats
  • Receptors, Cytoplasmic and Nuclear / biosynthesis
  • Receptors, Cytoplasmic and Nuclear / chemistry*
  • Receptors, Cytoplasmic and Nuclear / genetics
  • Receptors, Cytoplasmic and Nuclear / metabolism
  • Receptors, Cytoplasmic and Nuclear / therapeutic use*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transcription Factors / physiology
  • Triglycerides / metabolism

Substances

  • Bile Acids and Salts
  • Receptors, Cytoplasmic and Nuclear
  • Transcription Factors
  • Triglycerides
  • farnesoid X-activated receptor
  • Glucose