Bile acid–sensing receptor (BAR)

Bile acid–sensing receptors (BARs) are a group of receptors that recognize bile acids as signaling molecules to regulate systemic metabolism, energy balance, and hepatic function. The family includes the nuclear farnesoid X receptor (FXR) and the membrane-bound G protein-coupled bile acid receptor 1 (GPBAR1, also known as TGR5) (Fiorucci et al., 2019, Trends in Pharmacological Sciences). FXR is primarily expressed in the liver and intestine, where it acts as a master regulator of bile acid homeostasis by inhibiting synthesis and promoting transport, while also influencing lipid and glucose metabolism (Makishima et al., 1999, Science). TGR5 is found in tissues such as the gallbladder, intestine, and brown adipose tissue, where its activation stimulates the release of glucagon-like peptide-1 (GLP-1) and enhances energy expenditure (Maruyama et al., 2002, BBRC). These receptors are key therapeutic targets for treating chronic liver diseases, such as primary biliary cholangitis (PBC) and nonalcoholic steatohepatitis (NASH), as well as metabolic disorders like type 2 diabetes (Trauner et al., 2017, Journal of Hepatology). While drugs like obeticholic acid have shown efficacy in clinical settings, challenges such as treatment-induced pruritus and changes in serum lipid profiles remain significant considerations for drug development (Siddiqui et al., 2020, Hepatology).

Other names

Bile acid receptorBARsFarnesoid X receptorG protein-coupled bile acid receptor 1TGR5FXRGPBAR1NR1H4

Agonism of nuclear bile acid receptors (e.g., FXR) modulates gene expression to inhibit bile acid synthesis and promote transport, while activation of membrane-bound receptors (e.g., TGR5) triggers intracellular signaling cascades such as cAMP production to stimulate GLP-1 release and metabolic activity (Fiorucci et al., 2019, Trends in Pharmacological Sciences; De Aguiar Vallim et al., 2013, Physiological Reviews).