FXR agonists as therapeutic agents for non-alcoholic fatty liver disease

Curr Atheroscler Rep. 2015 Apr;17(4):500. doi: 10.1007/s11883-015-0500-2.

Abstract

Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome and a risk factor for both cardiovascular and hepatic related morbidity and mortality. The increasing prevalence of this disease requires novel therapeutic approaches to prevent disease progression. Farnesoid X receptors are bile acid receptors with roles in lipid, glucose, and energy homeostasis. Synthetic farnesoid X receptor (FXR) agonists have been developed to specifically target these receptors for therapeutic use in NAFLD patients. Here, we present a review of bile acid physiology and how agonism of FXR receptors has been examined in pre-clinical and clinical NAFLD. Early evidence suggests a potential role for synthetic FXR agonists in the management of NAFLD; however, additional studies are needed to clarify their effects on lipid and glucose parameters in humans.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Bile Acids and Salts / metabolism
  • Chenodeoxycholic Acid / analogs & derivatives*
  • Chenodeoxycholic Acid / therapeutic use
  • Cholagogues and Choleretics / therapeutic use*
  • Fatty Liver, Alcoholic / drug therapy
  • Humans
  • NF-kappa B / metabolism
  • Non-alcoholic Fatty Liver Disease / drug therapy*
  • Non-alcoholic Fatty Liver Disease / metabolism
  • PPAR alpha / metabolism
  • Phosphoenolpyruvate Carboxykinase (ATP) / metabolism
  • Receptors, Cytoplasmic and Nuclear / agonists*
  • Receptors, Cytoplasmic and Nuclear / metabolism
  • Sterol Regulatory Element Binding Protein 1 / metabolism
  • Ursodeoxycholic Acid / therapeutic use*

Substances

  • Bile Acids and Salts
  • Cholagogues and Choleretics
  • NF-kappa B
  • PPAR alpha
  • Receptors, Cytoplasmic and Nuclear
  • SREBF1 protein, human
  • Sterol Regulatory Element Binding Protein 1
  • obeticholic acid
  • farnesoid X-activated receptor
  • Chenodeoxycholic Acid
  • Ursodeoxycholic Acid
  • PCK2 protein, human
  • Phosphoenolpyruvate Carboxykinase (ATP)