Nuclear receptor subfamily 1 group H member 4 (Farnesoid X receptor) (FXR)

The Nuclear receptor subfamily 1 group H member 4 (NR1H4), commonly known as the Farnesoid X receptor (FXR), is a ligand-activated transcription factor that serves as the primary sensor for bile acids in the body [1, 7]. Predominantly expressed in the liver and intestine, FXR plays a critical role in maintaining bile acid homeostasis by regulating genes involved in their synthesis, transport, and enterohepatic circulation [5, 9]. Upon activation by bile acids or synthetic agonists, FXR forms a heterodimer with the Retinoid X receptor (RXR) to modulate the expression of target genes such as BSEP (bile salt export pump) and SHP (small heterodimer partner), the latter of which represses the rate-limiting enzyme in bile acid synthesis, CYP7A1 [7, 11]. Beyond bile acid metabolism, FXR is a key regulator of lipid and glucose homeostasis, influencing triglyceride levels and insulin sensitivity [4, 8]. Due to its central role in metabolic and hepatobiliary pathways, FXR is a major therapeutic target for conditions such as primary biliary cholangitis (PBC), non-alcoholic steatohepatitis (NASH), and various cholestatic disorders [8, 10]. While drugs like obeticholic acid have been approved for clinical use, the development of FXR agonists faces challenges such as drug-induced pruritus and adverse effects on plasma lipid profiles, specifically the elevation of LDL cholesterol [4, 11].

Other names

Bile acid receptorBARFarnesoid X-activated receptorRXR-interacting protein 14RIP14HRR1HRR-1Farnesol receptor HRR-1NR1H4

Agonism