Retinoic acid-related orphan receptor α regulates diurnal rhythm and fasting induction of sterol 12α-hydroxylase in bile acid synthesis

Abstract

Background: Sterol 12α-hydroxylase catalyzes cholic acid synthesis. RORα is a cholesterol-activated and fasting-induced nuclear receptor and core clock gene. Results: Upon fasting, glucagon/PKA phosphorylated and stabilized RORα protein to induce CYP8B1 and diurnal rhythm. Conclusion: RORα is a key regulator of CYP8B1 that regulates bile acid and cholesterol homeostasis. Significance: Antagonizing RORα activity may be a therapeutic strategy for treating non-alcoholic fatty liver disease and diabetes. © 2013 by The American Society for Biochemistry and Molecular Biology, Inc.