Bile acid transporters and related hepatic targets

Bile acid transporters and related hepatic targets comprise a complex network of proteins responsible for the synthesis, transport, and regulation of bile acids within the enterohepatic circulation [UniProt, 2023]. Key members include the Sodium/taurocholate cotransporting polypeptide (NTCP/SLC10A1) for hepatic uptake, the Bile salt export pump (BSEP/ABCB11) for canalicular secretion, and the Apical sodium-dependent bile acid transporter (ASBT/SLC10A2) for intestinal reabsorption [PubMed, PMID: 31513010]. This system also includes regulatory receptors such as the Farnesoid X receptor (FXR/NR1H4) and the G protein-coupled bile acid receptor (TGR5/GPBAR1), which modulate metabolic pathways and inflammatory responses [Nature Reviews Gastroenterology & Hepatology, 2020]. Dysregulation of these targets is central to the pathogenesis of cholestatic liver diseases, metabolic disorders like nonalcoholic steatohepatitis (NASH), and viral infections such as Hepatitis B and D [Journal of Hepatology, 2021]. Pharmacological modulation of these targets—through inhibition of transporters (e.g., Odevixibat for ASBT) or activation of regulatory receptors (e.g., Obeticholic acid for FXR)—offers therapeutic strategies for managing bile acid-mediated liver injury and systemic metabolic dysfunction [FDA, 2016; 2021]. Recent clinical successes with ASBT inhibitors and FXR agonists have validated this network as a critical therapeutic axis in hepatology [The Lancet Gastroenterology & Hepatology, 2022].

Other names

Bile acid transport systemHepatobiliary transportersBile acid signaling pathwayEnterohepatic bile acid transporters

Pharmacological intervention involves inhibiting ileal reabsorption via ASBT inhibitors to reduce the bile acid pool, activating the nuclear receptor FXR to downregulate bile acid synthesis and promote secretion, and blocking the NTCP transporter to prevent viral entry and hepatic bile acid uptake [PubMed, PMID: 31513010; Nature Reviews Drug Discovery, 2020].