Anti-inflammatory and metabolic actions of FXR: insights into molecular mechanisms

Biochim Biophys Acta. 2012 Nov;1821(11):1443-52. doi: 10.1016/j.bbalip.2012.07.004. Epub 2012 Jul 20.


The farnesoid X receptor (FXR) is a ligand-activated transcription factor belonging to the nuclear receptor (NR) superfamily. FXR plays an important role in positively regulating genes (transactivation) involved in bile acid homeostasis, fat and glucose metabolism. Recently, it has become clear that an additional important role for FXR consists of downregulating genes involved in inflammation. Because of this broad spectrum of regulated genes, therapeutically targeting FXR with full agonists will likely result in adverse side effects, in line with what is described for other NRs. It may therefore be necessary to develop selective FXR modulators. However, the molecular mechanisms that distinguish between FXR-mediated transactivation and transrepression are currently unknown. For other NRs, post-translational modifications such as SUMOylation and phosphorylation have been reported to be unique to either transactivation or transrepression. Here, we review current knowledge on post-translational regulation of FXR with respect to transactivation and transrepression. Ultimately, increased understanding of the different mechanisms of transactivation and transrepression of nuclear receptors will aid in the development of NR drugs with fewer side effects.

Publication types

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

MeSH terms

  • Anti-Inflammatory Agents / pharmacology*
  • Bile Acids and Salts / metabolism*
  • Humans
  • Inflammation / drug therapy*
  • Protein Processing, Post-Translational
  • RNA-Binding Proteins / metabolism*


  • Anti-Inflammatory Agents
  • Bile Acids and Salts
  • FXR1 protein, human
  • RNA-Binding Proteins