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

Yoshihiro Konno, Masahiko Negishi, Susumu Kodama

Research output: Contribution to journalReview article

104 Citations (Scopus)

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 γ coactivator 1a (PGC 1α) 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.

Original languageEnglish
Pages (from-to)8-13
Number of pages6
JournalDrug Metabolism and Pharmacokinetics
Volume23
Issue number1
DOIs
Publication statusPublished - 2008
Externally publishedYes

Fingerprint

Cytoplasmic and Nuclear Receptors
Energy Metabolism
Liver
Xenobiotics
Transcription Factors
Receptor Cross-Talk
Drug Receptors
Cyclic AMP Response Element-Binding Protein
Lipogenesis
Peroxisome Proliferator-Activated Receptors
Gluconeogenesis
pregnane X receptor
constitutive androstane receptor
Phenobarbital
Thyroid Hormones
varespladib methyl
Genes
Fatty Acids
Hormones
Enzymes

Keywords

  • Constitutive active/androstane receptor (CAR)
  • Cytochrome P450
  • Drug metabolism
  • Gluconeogenesis
  • Lipid metabolism
  • Pregnane X receptor (PXR)
  • Thyroid hormone

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology
  • Pharmaceutical Science
  • Medicine(all)

Cite this

The roles of nuclear receptors CAR and PXR in hepatic energy metabolism. / Konno, Yoshihiro; Negishi, Masahiko; Kodama, Susumu.

In: Drug Metabolism and Pharmacokinetics, Vol. 23, No. 1, 2008, p. 8-13.

Research output: Contribution to journalReview article

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