Bile acid metabolism regulation

Bile acid metabolism regulation is a complex physiological system that maintains the balance of bile acids within the enterohepatic circulation, serving critical roles in lipid digestion and systemic signaling [1][2]. The process is primarily governed by the farnesoid X receptor (FXR), which acts as a molecular sensor for bile acids to regulate their synthesis, transport, and detoxification [1][3]. When bile acid levels are high, FXR suppresses the rate-limiting enzyme cholesterol 7α-hydroxylase (CYP7A1) via the induction of fibroblast growth factor 19 (FGF19) [3][5]. Beyond the liver, bile acids interact with the G protein-coupled receptor TGR5 to modulate glucose metabolism and inflammatory responses [3]. Dysregulation of this metabolic control is central to the development of cholestatic diseases like primary biliary cholangitis and metabolic disorders such as non-alcoholic steatohepatitis (NASH) [2][4]. Therapeutic interventions target various nodes of this regulation, including FXR agonists to reduce bile acid pools and ASBT inhibitors to prevent intestinal reabsorption, aiming to alleviate cholestasis and improve metabolic health [4][5].

Other names

Bile acid homeostasisBile acid signaling pathwayEnterohepatic circulation of bile acids

The regulation of bile acid metabolism is achieved through several mechanisms: activation of the farnesoid X receptor (FXR) which induces FGF19 to suppress hepatic CYP7A1-mediated bile acid synthesis; inhibition of the apical sodium-dependent bile acid transporter (ASBT) to reduce enterohepatic recirculation; and activation of the TGR5 receptor to enhance GLP-1 secretion and energy expenditure [1][3][5].