Pregnane X Receptor and Constitutive Androstane Receptor at the Crossroads of Drug Metabolism and Energy Metabolism
Authors:
- 1 December 2010
- journal article
- review article
- Published by Elsevier in Drug Metabolism and Disposition
- Vol. 38 (12) , 2091-2095
Abstract
The pregnane X receptor (PXR) and the constitutive androstane receptor (CAR) are two closely related and liver-enriched nuclear hormone receptors originally defined as xenobiotic receptors. PXR and CAR regulate the transcription of drug-metabolizing enzymes and transporters, which are essential in protecting our bodies from the accumulation of harmful chemicals. An increasing body of evidence suggests that PXR and CAR also have an endobiotic function that impacts energy homeostasis through the regulation of glucose and lipids metabolism. Of note and in contrast, disruptions of energy homeostasis, such as those observed in obesity and diabetes, also have a major impact on drug metabolism. This review will focus on recent progress in our understanding of the integral role of PXR and CAR in drug metabolism and energy homeostasis.Keywords
This publication has 67 references indexed in Scilit:
- Activation of nuclear receptor CAR ameliorates diabetes and fatty liver diseaseProceedings of the National Academy of Sciences, 2009
- Hepatic Cytochrome P450 Enzyme Alterations in Humans with Progressive Stages of Nonalcoholic Fatty Liver DiseaseDrug Metabolism and Disposition, 2009
- The Constitutive Androstane Receptor Is an Anti-obesity Nuclear Receptor That Improves Insulin SensitivityJournal of Biological Chemistry, 2009
- Constitutive androstane receptor mediates the induction of drug metabolism in mouse models of type 1 diabetes†Hepatology, 2009
- Unsaturated fatty acid regulation of cytochrome P450 expression via a CAR-dependent pathwayBiochemical Journal, 2008
- Human nuclear pregnane X receptor cross-talk with CREB to repress cAMP activation of the glucose-6-phosphatase geneBiochemical Journal, 2007
- Nuclear Pregnane X Receptor Cross-talk with FoxA2 to Mediate Drug-induced Regulation of Lipid Metabolism in Fasting Mouse LiverJournal of Biological Chemistry, 2007
- In the regulation of cytochrome P450 genes, phenobarbital targets LKB1 for necessary activation of AMP-activated protein kinaseProceedings of the National Academy of Sciences, 2007
- A physiological role of AMP-activated protein kinase in phenobarbital-mediated constitutive androstane receptor activation and CYP2B inductionBiochemical Journal, 2007
- Regulation of Constitutive Androstane Receptor and Its Target Genes by Fasting, cAMP, Hepatocyte Nuclear Factor α, and the Coactivator Peroxisome Proliferator-activated Receptor γ Coactivator-1αJournal of Biological Chemistry, 2006