Bile-acid-activated receptors: targeting TGR5 and farnesoid-X-receptor in lipid and glucose disorders

Trends Pharmacol Sci. 2009 Nov;30(11):570-80. doi: 10.1016/ Epub 2009 Sep 14.


Bile acids are a family of steroid molecules generated in the liver by cholesterol oxidation. In addition to their role in nutrient absorption, bile acids are signaling molecules that exert genomic and non-genomic effects by activating TGR5 (M-BAR, GP-BAR1 or BG37) a G-protein-coupled receptor, and farnesoid X receptor (FXR), a member of the nuclear hormone receptor superfamily. Ligands for these receptors might be beneficial in treating disorders of lipid and glucose homeostasis. TGR5 ligands decrease blood glucose levels and increase energy expenditure by promoting intracellular thyroid hormone activation in thermogenically competent tissues. FXR agonists repress the synthesis of endogenous bile acids and reduce triglyceride, cholesterol and glucose plasma levels and are currently being tested in nonalcoholic steatohepatitis. FXR modulators are being developed to target selective gene clusters and avoid the negative impact of FXR on HDL biosynthesis. The development of dual FXR and TGR5 ligands could provide new opportunities for the treatment of lipid and glucose disorders.

Publication types

  • Review

MeSH terms

  • Animals
  • Bile Acids and Salts / metabolism
  • Blood Glucose / drug effects
  • Blood Glucose / metabolism
  • Drug Delivery Systems*
  • Dyslipidemias / drug therapy
  • Dyslipidemias / physiopathology
  • Glucose Metabolism Disorders / drug therapy
  • Glucose Metabolism Disorders / physiopathology
  • Homeostasis / drug effects
  • Humans
  • Ligands
  • Receptors, Cytoplasmic and Nuclear / drug effects*
  • Receptors, Cytoplasmic and Nuclear / metabolism
  • Receptors, G-Protein-Coupled / drug effects*
  • Receptors, G-Protein-Coupled / metabolism


  • Bile Acids and Salts
  • Blood Glucose
  • GPBAR1 protein, human
  • Ligands
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, G-Protein-Coupled
  • farnesoid X-activated receptor