FXR, a bile acid receptor and biological sensor

Bile acid synthesis is a major pathway for cholesterol disposal and thus represents a potential therapeutic target pathway for the treatment of hypercholesterolemia. Recently, the nuclear farnesoid X receptor (FXR) was identified as a bile acid receptor and biological sensor fbr the regulation of bile acid biosynthesis. FXR was shown to regulate cholesterol metabolism in two ways: (1) Chenodeoxycholic acid (CDCA), a primary bite acid, binds directly to and activates FXR, which then mediates the feedback suppression by bile acids of cholesterol 7 alpha -hydroxylase (CYP7A1), the rate-limiting enzyme in bile acid biosynthesis fi om cholesterol; and (2) FXR participates in the activation of intestinal bile acid binding protein (IBABP), which is involved in the enterohepatic circulation of bile acids. Thus FXR constitutes a potential therapeutic target that can be modulated to enhance the removal of cholesterol from the body (Trends Cardiovasc Med 2000;10:30-35). (C) 2000, Elsevier Science Inc.