Farnesoid X receptor (FXR) and Bile Acid Transporter (BAT) (FXR/BAT)

The Farnesoid X receptor (FXR) and bile acid transporters (BATs) are integral components of the enterohepatic circulation system that maintains bile acid homeostasis. FXR (NR1H4) is a nuclear receptor that serves as the primary sensor for intracellular bile acids, regulating genes involved in their synthesis, secretion, and reabsorption [UniProt: Q96RI1]. Bile acid transporters, such as the apical sodium-dependent bile acid transporter (ASBT/SLC10A2) and the bile salt export pump (BSEP/ABCB11), facilitate the movement of bile acids between the liver, gallbladder, and intestine [UniProt: Q12908]. Dysregulation of this system leads to toxic bile acid accumulation, contributing to cholestatic liver diseases and metabolic disorders like non-alcoholic steatohepatitis (NASH). Therapeutic strategies include FXR agonists to reduce bile acid production and ASBT inhibitors to interrupt the recycling of bile acids from the gut. While effective, these therapies are often associated with side effects such as pruritus and changes in lipid metabolism, which remain significant clinical challenges.

Other names

NR1H4Bile acid receptorBARSLC10A2ASBTSLC10A1NTCPABCB11BSEPSLC51AOST-alphaSLC51BOST-beta

FXR agonists activate the Farnesoid X receptor to suppress bile acid synthesis via the SHP-mediated inhibition of CYP7A1 and the induction of FGF19 [PubMed: 25183558]. Bile acid transporter inhibitors, specifically ASBT inhibitors, block the apical sodium-dependent bile acid transporter in the terminal ileum, preventing the reuptake of bile acids and promoting their excretion into the feces [StatPearls: NBK547745].