Nuclear receptor regulation of bile acid synthesis

From LipidomicsWiki

The enterohepatic circulation of bile acids is an important physiological process that generates bile flow and feedback controls bile acid synthesis. The rate of bile acid synthesis, bile acid composition, and bile acid pool size vary significantly depending on the species, sexes, genetics, pathophysiological conditions, and environmental factors such as diets and drugs (Carey et al. 1994; Hofmann 1999). Many nuclear receptors have been found to play pivotal roles in regulating transcription of the genes involved in bile acid synthesis (Chiang 2002, 2003). In general, hydrophobic bile acids (CA, CDCA, DCA and LCA) are potent inhibitors of bile acid biosynthesis, whereas hydrophilic bile acids, such as 7β-bile acids, e.g. ursodeoxycholic acid and β-muricholic acids are not. Chiang and coworkers proposed that bile acids might bind to a bile acid receptor that interacts with a bile acid responsive protein and inhibits its trans-activation of the CYP7A1 gene (Chiang 1994; 1998). This nuclear receptor-mediated mechanism is supported by recent identification of several nuclear receptors as bile acid receptors (Chiang 2002, 2003, 1994)

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