Fig. 5.

FXR negatively feedback regulation of BAs synthesis. Hepatic cholesterol results from HMGR mediated conversion of acetate. BAs are synthesized from cholesterol by a series of enzymes including the initial and rate-limiting CYP7A1 in hepatocytes. BAs bind to FXR in the nucleus. In hepatocytes, FXR induces SHP, which inhibits transcription of CYP7A1 and BAs synthesis. Intestinal FXR induces FGF15, which circulates to the liver and binds to hepatic FGFR4, inhibiting transcription of CYP7A1 and BAs synthesis. ASBT expressed in the brush border of terminal ileal enterocytes mediate approximately 95% of BAs reabsorption. ABCG5/8 secretes cholesterol from hepatocytes into the bile. The cholesterol is transferred to the brush border membrane of enterocytes via bile salt micelles. Then, ABCG5/8 mediates biliary and cholesterol from the brush border membrane back into the gut lumen for excretion.