Pregnane X receptor and constitutive androstane receptor at the crossroads of drug metabolism and energy metabolism

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.

Fig. 1.

Summary of the major interactions between drug metabolism and energy metabolism and the central roles of PXR and CAR in these cross-talks. Note that the drug metabolism and energy status can be affected by pathophysiological conditions, such as obesity, diabetes, and fatty liver. DME, drug-metabolizing enzymes; FFA, free fatty acids; HNF4α, hepatocyte nuclear factor 4α.