FXR in liver physiology: Multiple faces to regulate liver metabolism

Area of Science:

• Metabolic regulation
• Hepatology
• Nuclear receptor signaling

Background:

• The liver acts as a central metabolic hub, processing nutrients and coordinating metabolic outputs.
• Bile acids, released after food intake, are sensed by the Farnesoid X receptor (FXR) in the liver and intestine.
• FXR plays a key role in coordinating postprandial nutrient disposal through a network of nuclear receptors.

Purpose of the Study:

• To summarize and update the classical roles of FXR in integrating the feeding state response.
• To discuss emerging FXR effects on amino acid, protein metabolism, autophagy, and inflammation.
• To review recent findings on FXR signaling modulation by posttranslational modifications and isoforms.

Main Methods:

• Literature review and synthesis of existing research on FXR.
• Analysis of FXR's role in metabolic pathways.
• Discussion of FXR signaling regulation and clinical implications.

Main Results:

• FXR is a central integrator of feeding responses, orchestrating carbohydrate, lipid, protein, and bile acid metabolism.
• Emerging evidence highlights FXR's influence on amino acid metabolism, protein turnover, autophagy, and inflammation.
• FXR signaling is modulated by posttranslational modifications and different isoforms, impacting its function.

Conclusions:

• FXR is a critical regulator of nutrient metabolism and the feeding response.
• Understanding novel FXR functions and regulatory mechanisms is crucial for therapeutic targeting.
• Modifications and isoforms of FXR are important considerations for pharmaceutical applications.