Homeostatic Control of Bile Acid Biosynthesis and Transport By Nuclear Receptors

摘要

It is well established that bile acids regulate the expression of a number of biosynthetic enzymes that are essential for catabolism of cholesterol and maintenance of bile acid homeostasis1"3. These include cholesterol 7a-hydroxylase (CYP7A1), 7a-cholesterol 12a-hydroxylase (CYP8B1), and 7a,12a-hydroxycho-lesterol 27-hydroxylase (CYP27A1), enzymes that contribute to the neutral pathway of bile acid biosynthesis and the oxysterol (24-, 25- and 27-) hydroxy-cholesterol 7a-hydroxylases, CYP7B1 and CYP39A1, that catalyse the production of chenodeoxycholic acid in the acidic pathway of bile acid synthesis. Bile acids also regulate the expression of a number of transport proteins including the sodium taurocholate cotransporting polypeptide (NTCP)4, bile salt export pump (BSEP, also called ABCB11)5, liver fatty acid binding protein (L-FABP)6 and ileal bile acid binding protein (I-BABP)7. Accumulating evidence derived from independent studies has established that the genes encoding these enzymes and transporters are regulated by several nuclear receptors that are activated by bile acids and other ligands.