Physiological Functions and Pathological Roles of PXR.

The pregnane X receptor (PXR, NR1I2), a member of the nuclear receptor superfamily, mainly acts as a ligand-activated transcription factor. PXR is predominantly expressed in the liver and intestines, though it is also present at lower levels in various other tissues. PXR is known for its critical role in regulating the metabolism of various chemical substances, including dietary, xenobiotic, and endogenous compounds. As a master regulator of detoxification pathways, PXR modulates the expression of drug-metabolizing enzymes and transporters, contributing to the clearance of potentially harmful compounds. Beyond this classic role, emerging evidence highlights a broader role for PXR on metabolic homeostasis and its involvement in several physiological processes and diseases. This review provides a comprehensive overview of PXR functions across several key metabolic pathways. PXR influences glucose homeostasis by modulating the expression of genes involved in glucose production and insulin sensitivity, highlighting its important role in glucose regulation. PXR regulates the synthesis, breakdown, and transport of lipids, and regulates the expression of genes involved in fatty acid oxidation and cholesterol homeostasis. PXR is involved in inflammatory diseases by modulating the expression of inflammatory cytokines and immune responses, indicating that PXR is a potential target for therapeutic interventions in inflammatory disorders. Furthermore, we discuss PXR function on the regulation of vitamin, bone, and bile acid metabolism.