FXR, a bile acid receptor and biological sensor

Bile acid synthesis is a major pathway for cholesterol disposal and thus re presents a potential therapeutic target pathway for the treatment of hyperc holesterolemia. Recently, the nuclear farnesoid X receptor (FXR) was identi fied as a bile acid receptor and biological sensor fbr the regulation of bi le acid biosynthesis. FXR was shown to regulate cholesterol metabolism in t wo ways: (1) Chenodeoxycholic acid (CDCA), a primary bite acid, binds direc tly to and activates FXR, which then mediates the feedback suppression by b ile acids of cholesterol 7 alpha -hydroxylase (CYP7A1), the rate-limiting e nzyme in bile acid biosynthesis fi om cholesterol; and (2) FXR participates in the activation of intestinal bile acid binding protein (IBABP), which i s involved in the enterohepatic circulation of bile acids. Thus FXR constit utes a potential therapeutic target that can be modulated to enhance the re moval of cholesterol from the body (Trends Cardiovasc Med 2000;10:30-35). ( C) 2000, Elsevier Science Inc.