Tissue-specific actions of FXR in metabolism and cancer

Raffaella Maria Gadaleta, Marica Cariello, Carlo Sabbà, Antonio Moschetta

Research output: Contribution to journalArticlepeer-review

Abstract

The nuclear Farnesoid X Receptor (FXR) is a transcription factor critically involved in metabolic homeostasis in the gut-liver axis. FXR activity is mediated by hormonal and dietary signals and driven by bile acids (BAs), which are the natural FXR ligands. Given the great physiological importance in BA homeostasis, as well as in the regulation of glucose and lipid metabolism, FXR plays a pivotal role in the pathogenesis of a wide range of disease of the liver, biliary tract and intestine, including hepatic and colorectal cancer. In the last years several studies have shown the relative FXR tissue-specific importance, highlighting synergism and additive effects in the liver and intestine. Gain- and loss-of-FXR-function mouse models have been generated in order to identify the biological processes and the molecular FXR targets. Taking advantage of the knowledge on the structure-activity relationship of BAs for FXR, semi-synthetic and synthetic molecules have been generated to obtain more selective and powerful FXR activators than BAs. This article is part of a Special Issue entitled: Linking transcription to physiology in lipodomics.

Original languageEnglish
Pages (from-to)30-39
Number of pages10
JournalBiochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
Volume1851
Issue number1
DOIs
Publication statusPublished - 2015

Keywords

  • Bile acid homeostasis
  • Farnesoid X receptor
  • Gut-liver axis
  • Hepatic and colorectal carcinogenesis
  • Selective FXR ligands

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Medicine(all)

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