The roles of nuclear receptors CAR and PXR in hepatic energy metabolism

Drug Metab Pharmacokinet. 2008;23(1):8-13. doi: 10.2133/dmpk.23.8.

Abstract

Nuclear receptors constitutive active/androstane receptor (CAR) and pregnane X receptor (PXR) were originally characterized as transcription factors regulating the hepatic genes that encode drug metabolizing enzymes. Recent works have now revealed that these nuclear receptors also play the critical roles in modulating hepatic energy metabolism. While CAR and PXR directly bind to their response sequences phenobarbital-responsive enhancer module (PBREM) and xenobiotic responsive enhancer module (XREM) in the promoter of target genes to increase drug metabolism, the receptors also cross talk with various hormone responsive transcription factors such as forkhead box O1 (FoxO1), forkhead box A2 (FoxA2), cAMP-response element binding protein, and peroxisome proliferator activated receptor gamma coactivator 1alpha (PGC 1alpha) to decrease energy metabolism through down-regulating gluconeogenesis, fatty acid oxidation and ketogenesis and up-regulating lipogenesis. In addition, CAR modulates thyroid hormone activity by regulating type 1 deiodinase in the regenerating liver. Thus, CAR and PXR are now placed at the crossroad where both xenobiotics and endogenous stimuli co-regulate liver function.

Publication types

  • Review

MeSH terms

  • Animals
  • Cell Nucleus / genetics
  • Cell Nucleus / metabolism*
  • Energy Metabolism / genetics
  • Energy Metabolism / physiology*
  • Humans
  • Liver / metabolism*
  • Pregnane X Receptor
  • Receptor Cross-Talk / physiology*
  • Receptors, Cytoplasmic and Nuclear / genetics
  • Receptors, Cytoplasmic and Nuclear / physiology*
  • Receptors, Steroid / genetics
  • Receptors, Steroid / physiology*
  • Transcription Factors / genetics
  • Transcription Factors / physiology*

Substances

  • Pregnane X Receptor
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, Steroid
  • Transcription Factors
  • constitutive androstane receptor