Circadian dysregulation disrupts bile acid homeostasis.

ABSTRACT:

Background

Bile acids are potentially toxic compounds and their levels of hepatic production, uptake and export are tightly regulated by many inputs, including circadian rhythm. We tested the impact of disrupting the peripheral circadian clock on integral steps of bile acid homeostasis.

Methodology/principal findings

Both restricted feeding, which phase shifts peripheral clocks, and genetic ablation in Per1(-/-)/Per2(-/-) (PERDKO) mice disrupted normal bile acid control and resulted in hepatic cholestasis. Restricted feeding caused a dramatic, transient elevation in hepatic bile acid levels that was associated with activation of the xenobiotic receptors CAR and PXR and elevated serum aspartate aminotransferase (AST), indicative of liver damage. In the PERDKO mice, serum bile

SUBMITTER: Ma K 

PROVIDER: S-EPMC2730029 | biostudies-literature | 2009 Aug

REPOSITORIES: biostudies-literature