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Circadian Homeostasis of Liver Metabolism Suppresses Hepatocarcinogenesis
Daily Metabolic Balance in the Liver May Help Prevent Liver Cancer
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Abstract
Chronic jet lag induces spontaneous hepatocellular carcinoma (HCC) in wild-type mice.
- Chronic jet lag is associated with the development of non-alcoholic fatty liver disease (NAFLD) that progresses to steatohepatitis and fibrosis before HCC occurs.
- Genome-wide gene deregulation and global liver metabolic dysfunction are observed as key drivers in the progression towards HCC.
- The pathways most affected include cholesterol and bile acid metabolism, as well as xenobiotic metabolism.
- Ablation of the farnesoid X receptor leads to increased bile acid levels and enhances the risk of jet-lag-induced HCC.
- Loss of the constitutive androstane receptor (CAR) inhibits the progression from NAFLD to liver cancer.
- Circadian disruption activates CAR, contributing to cholestasis and metabolic dysfunction.
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