Regulatory network of lipid-sensing nuclear receptors: roles for CAR, PXR, LXR, and FXR

Arch Biochem Biophys. 2005 Jan 15;433(2):387-96. doi: 10.1016/j.abb.2004.08.030.

Abstract

Cloning and characterization of the orphan nuclear receptors constitutive androstane receptor (CAR, NR1I3) and pregnane X receptor (PXR, NR1I2) led to major breakthroughs in studying drug-mediated transcriptional induction of drug-metabolizing cytochromes P450 (CYPs). More recently, additional roles for CAR and PXR have been discovered. As examples, these xenosensors are involved in the homeostasis of cholesterol, bile acids, bilirubin, and other endogenous hydrophobic molecules in the liver: CAR and PXR thus form an intricate regulatory network with other members of the nuclear receptor superfamily, foremost the cholesterol-sensing liver X receptor (LXR, NR1H2/3) and the bile-acid-activated farnesoid X receptor (FXR, NR1H4). In this review, functional interactions between these nuclear receptors as well as the consequences on physiology and pathophysiology of the liver are discussed.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Bile Acids and Salts / metabolism
  • Bilirubin / metabolism
  • Cell Nucleus / metabolism
  • Cholesterol / metabolism
  • Cloning, Molecular
  • Constitutive Androstane Receptor
  • Cytochrome P-450 Enzyme System / genetics
  • Cytochrome P-450 Enzyme System / metabolism
  • Cytochrome P-450 Enzyme System / physiology
  • DNA-Binding Proteins / metabolism*
  • Humans
  • Lipid Metabolism*
  • Liver / metabolism
  • Liver X Receptors
  • Models, Biological
  • Orphan Nuclear Receptors
  • Phylogeny
  • Pregnane X Receptor
  • Receptors, Cytoplasmic and Nuclear / metabolism*
  • Receptors, Steroid / metabolism*
  • Species Specificity
  • Transcription Factors / metabolism*
  • Xenobiotics / metabolism

Substances

  • Bile Acids and Salts
  • Constitutive Androstane Receptor
  • DNA-Binding Proteins
  • Liver X Receptors
  • NR1H2 protein, human
  • NR1I2 protein, human
  • NR1I3 protein, human
  • Orphan Nuclear Receptors
  • Pregnane X Receptor
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, Steroid
  • Transcription Factors
  • Xenobiotics
  • farnesoid X-activated receptor
  • Cytochrome P-450 Enzyme System
  • Cholesterol
  • Bilirubin