The xenobiotic receptors PXR and CAR in liver physiology, an update

Area of Science:

• Hepatology and molecular endocrinology.
• Nuclear receptor signaling pathways.

Background:

• Pregnane X receptor (PXR) and constitutive androstane receptor (CAR) are key nuclear receptors involved in xenobiotic detoxification.
• These receptors regulate drug-metabolizing enzymes and transporters, which also handle endogenous chemicals (endobiotics).
• Both PXR and CAR are highly expressed in the liver, suggesting significant roles in hepatic pathophysiology.

Purpose of the Study:

• To review recent advancements in understanding the physiological functions of PXR and CAR within the liver.
• To explore the impact of PXR and CAR on endobiotic homeostasis and liver health.
• To summarize the known roles of these receptors in liver metabolism and disease.

Main Methods:

• Literature review of recent studies on PXR and CAR in liver physiology.
• Analysis of research investigating the regulation of drug-metabolizing enzymes and transporters by PXR and CAR.
• Synthesis of findings related to PXR and CAR involvement in energy metabolism, bile acid homeostasis, and cell proliferation.

Main Results:

• PXR and CAR play critical roles in maintaining the homeostasis of both xenobiotics and endobiotics in the liver.
• Emerging evidence links PXR and CAR activity to crucial liver functions including energy metabolism and bile acid regulation.
• These receptors influence liver cell proliferation and are implicated in various hepatic conditions.

Conclusions:

• PXR and CAR are integral to liver physiology, extending beyond xenobiotic metabolism to encompass endobiotic regulation.
• Their roles in energy metabolism, bile acid homeostasis, and cell proliferation underscore their importance in maintaining liver health.
• Further research into PXR and CAR functions offers potential therapeutic strategies for liver diseases.