Physiological Functions and Pathological Roles of PXR

Area of Science:

• Endocrinology
• Metabolic pathways
• Nuclear receptor signaling

Background:

• The pregnane X receptor (PXR, NR1I2) is a nuclear receptor primarily expressed in the liver and intestines.
• PXR functions as a ligand-activated transcription factor, crucial for xenobiotic and endogenous compound metabolism.
• It regulates drug-metabolizing enzymes and transporters, playing a vital role in detoxification.

Purpose of the Study:

• To provide a comprehensive review of PXR functions in key metabolic pathways.
• To highlight PXR's emerging roles beyond detoxification in metabolic homeostasis and disease.
• To explore PXR's involvement in glucose, lipid, inflammatory, vitamin, bone, and bile acid metabolism.

Main Methods:

• Literature review of PXR functions.
• Analysis of PXR's role in gene expression modulation.
• Synthesis of evidence on PXR's physiological and pathological involvement.

Main Results:

• PXR significantly influences glucose homeostasis, impacting glucose production and insulin sensitivity.
• PXR regulates lipid metabolism, including synthesis, breakdown, transport, and cholesterol homeostasis.
• PXR modulates inflammatory responses and is implicated in inflammatory diseases, vitamin, bone, and bile acid metabolism.

Conclusions:

• PXR is a master regulator of detoxification and a critical player in metabolic homeostasis.
• PXR's diverse roles in glucose, lipid, and inflammatory pathways present potential therapeutic targets.
• Further research into PXR's functions can advance understanding of metabolic diseases and inflammatory disorders.