Farnesoid X receptor
The bile acid receptor (BAR), also known as farnesoid X receptor (FXR) or NR1H4 (nuclear receptor subfamily 1, group H, member 4), is a nuclear receptor that is encoded by the "NR1H4" gene in humans. Function. FXR is expressed at high levels in the liver and intestine. Chenodeoxycholic acid and other bile acids are natural ligands for FXR. Similar to other nuclear receptors, when activated, FXR translocates to the cell nucleus, forms a dimer (in this case a heterodimer with RXR) and binds to hormone response elements on DNA, which up- or down-regulates the expression of  certain genes. One of the primary functions of FXR activation is the suppression of cholesterol 7 alpha-hydroxylase (CYP7A1), the rate-limiting enzyme in bile acid synthesis from cholesterol. FXR does not directly bind to the CYP7A1 promoter. Rather, FXR induces expression of small heterodimer partner (SHP), which then functions to inhibit transcription of the CYP7A1 gene. In this way, a negative feedback pathway is established in which synthesis of bile acids is inhibited when cellular levels are already high. FXR has also been found to be important in regulation of hepatic triglyceride levels. Specifically, FXR activation suppresses lipogenesis and  promotes free fatty acid oxidation by PPARα activation. Studies have also shown the FXR to regulate the expression and activity of epithelial transport proteins involved in fluid homeostasis in the intestine, such as the cystic fibrosis transmembrane conductance regulator (CFTR). Activation of FXR in diabetic mice reduces plasma glucose and improves insulin sensitivity, whereas inactivation of FXR has the opposite effect. Interactions. Farnesoid X receptor has been shown to interact with: Ligands. A number of ligands for FXR are known, of both natural and synthetic origin.