The farnesoid X receptor (FXR) as a new target in non-alcoholic steatohepatitis.
The farnesoid X receptor (FXR) is a member of the nuclear receptor superfamily that is mainly expressed in liver, intestine, kidney and adipose tissue. On activation by bile acids, FXR regulates a wide variety of target genes that are critically involved in the control of bile acid, lipid and glucose homeostasis. Thus, FXR appears to be a promising target for the treatment of non-alcoholic steatohepatitis (NASH). Notably, FXR activation inhibits hepatic de novo lipogenesis, increases insulin sensitivity and protects hepatocytes against bile acid-induced cytotoxicity. More recent data also indicate a critical role of FXR in liver regeneration and hepatocarcinogenesis. For this reason, the development of FXR agonists and/or modulators (SBARMs) may prove to be clinically useful for treating NASH. While preclinical studies in rodents support this hypothesis, clinical studies are still warranted in humans.
Cariou
B
B
Université de Nantes, Faculté de Médecine, 44093 Nantes cedex, France. betrand.cariou@univ-nantes.fr
D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism; D002874:Chromosome Mapping; D002881:Chromosomes, Human, Pair 12; D004268:DNA-Binding Proteins / Q000819:agonists / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D004195:Disease Models, Animal; D005234:Fatty Liver / Q000188:drug therapy / Q000503:physiopathology*; D006801:Humans; D007328:Insulin / Q000502:physiology; D007555:Isoxazoles / Q000627:therapeutic use; D008115:Liver Regeneration / Q000187:drug effects / Q000502:physiology; D051379:Mice; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D014157:Transcription Factors / Q000819:agonists / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D000099150:Receptor, Farnesoid X-Activated
D001647:Bile Acids and Salts; D004268:DNA-Binding Proteins; D007328:Insulin; D007555:Isoxazoles; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D000099150:Receptor, Farnesoid X-Activated