What is the Origin of Farnesoid X Receptor (FXR)?

FXR was initially identified in 1995 as an "orphan receptor," a member of the nuclear receptor superfamily whose natural ligand was unknown. It was originally named for its activation by farnesol, a farnesoid metabolite. Its true physiological role became clear in 1999 when bile acids, specifically chenodeoxycholic acid (CDCA), were identified as its high-affinity ligands. This discovery cemented its origin as the central bile acid receptor.

What is the Mechanism of Farnesoid X Receptor (FXR)?

When activated by binding to bile acids, the FXR protein forms a heterodimer with the Retinoid X Receptor (RXR) and translocates to the cell nucleus. This complex then binds to specific DNA sequences, which up- or down-regulates the expression of target genes involved in bile acid synthesis, transport, and metabolism. Crucially, FXR activation inhibits the rate-limiting enzyme in bile acid synthesis, CYP7A1, providing a negative feedback loop to prevent the buildup of potentially toxic bile acids in the liver.

Farnesoid X Receptor (FXR) ∞ Area

Farnesoid X Receptor (FXR)

Meaning

The Farnesoid X Receptor (FXR), scientifically known as NR1H4, is a nuclear receptor protein that functions as a master regulator of bile acid, lipid, and glucose homeostasis in the body. Expressed predominantly in the liver and intestine, FXR acts as a sensor for bile acids, which are its natural, endogenous ligands. Its primary role is to protect the liver and maintain metabolic balance by controlling the concentration and flow of bile acids throughout the enterohepatic circulation.