Regulation of Bile Acid Synthesis by the Nuclear Receptor Rev-erbα

Rev-erbalpha-deficient mice show a decreased bile acid synthesis rate and impaired excretion.

• Bile acid synthesis and CYP7A1 gene expression were altered in mice lacking Rev-erbalpha.
• CYP7A1, a key enzyme for bile acid production, was found to be less expressed in the livers of Rev-erbalpha-deficient mice.
• Overexpression of Rev-erbalpha in the liver led to an increase in CYP7A1 expression.
• Bile acid feeding intensified the suppression of CYP7A1 in Rev-erbalpha-deficient mice.
• Levels of two negative regulators of CYP7A1, SHP and E4BP4, were elevated in Rev-erbalpha-deficient mice.
• Circadian rhythms of liver CYP7A1, SHP, and E4BP4 messenger RNA levels were disrupted in the absence of Rev-erbalpha.

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