Research progress of pregnane X receptor as a therapeutic target for metabolic diseases

Pregnane X receptor (PXR), an important member of the nuclear receptor superfamily, serves as a sensor for xenobiotics and regulates the expression of drug-metabolizing enzymes and transporters. Recent studies have revealed that PXR is not only involved in drug metabolism and detoxification but also plays a critical role in glucose metabolism, lipid metabolism, bile acid homeostasis, and inflammatory regulation. As a ligand-activated transcription factor, PXR regulates downstream target genes expression, thus defending the body from xenobiotic and endogenous toxin attacks. PXR is associated with the development of a number of metabolic diseases such as obesity, type 2 diabetes mellitus, metabolic dysfunction-associated fatty liver disease, cholestatic liver diseases, cardiovascular diseases, etc. However, the regulatory mechanism of PXR in the context of glucose, lipid, cholesterol, and bile acid metabolism are complex and vary depending on nutritional status, species, and tissues. Therefore, developing drugs that selectively regulate PXR and its downstream signaling pathways may represent a promising strategy for treating metabolic diseases in the future. We review the structural and functional characteristics of PXR in the article, its transcriptional regulatory mechanisms, and the research progress of PXR as a therapeutic target for metabolic diseases. We summarize the research progress of drugs targeting PXR for the treatment of metabolic diseases, aiming to provide insights for future drug development targeting the PXR receptor for metabolic diseases treatment.