Farnesoid X Receptor Agonists and Other Bile Acid Signaling Strategies for Treatment of Liver Disease

Dig Dis. 2016;34(5):580-8. doi: 10.1159/000445268. Epub 2016 Jun 22.

Abstract

The intracellular nuclear receptor farnesoid X receptor (FXR) and the transmembrane G protein-coupled receptor 5 (TGR5) respond to bile acids (BAs) by activating transcriptional networks and/or signaling cascades. These cascades affect the expression of a great number of target genes relevant for BA, cholesterol, lipid and carbohydrate metabolism, as well as genes involved in inflammation, fibrosis and carcinogenesis. FXR activation in the liver tissue and beyond, such as the gut-liver axis, kidney and adipose tissue, plays a role in metabolic diseases. These BA receptors activators hold promise to become a new class of drugs to be used in the treatment of chronic liver disease, hepatocellular cancer and extrahepatic inflammatory and metabolic diseases. This review discusses the relevant BA receptors, the new drugs that target BA transport and signaling and their possible applications.

Publication types

  • Review

MeSH terms

  • Bile Acids and Salts / metabolism
  • Bile Acids and Salts / therapeutic use*
  • Humans
  • Inflammation
  • Liver Diseases / drug therapy*
  • Liver Diseases / genetics
  • Liver Neoplasms / drug therapy
  • Liver Neoplasms / genetics
  • Metabolic Diseases / drug therapy*
  • Metabolic Diseases / genetics
  • Molecular Targeted Therapy / methods*
  • Receptors, Cytoplasmic and Nuclear / agonists*
  • Receptors, Cytoplasmic and Nuclear / metabolism
  • Receptors, G-Protein-Coupled / metabolism
  • Signal Transduction / genetics

Substances

  • Bile Acids and Salts
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, G-Protein-Coupled
  • XCR1 protein, human
  • farnesoid X-activated receptor