Circadian clock disruption aggravates alcohol liver disease in an acute mouse model

Circadian rhythms are important for organisms to adapt to the environment and maintain homeostasis. Disruptions of circadian rhythms contribute to the occurrence, progression, and exacerbation of diseases, such as cancer, psychiatric disorders, and metabolic disorders. Alcohol-induced liver disease (ALD) is one of the most prevalent liver diseases. Disruptions of the circadian clock enhance the ALD symptoms using chronic mice models or genetic manipulated mice. However, chronic models are time consuming and clock gene deletions interfere with metabolisms. Here, we report that constant light (LL) condition significantly disrupted the circadian clock in an acute ALD model, resulting in aggravated ALD phenotypes in wild type mice. Comparative transcriptome analysis revealed that the alcohol feeding affected the circadian pathway, as well as metabolic pathways. The acute alcohol feeding plus the LL condition further interfered with metabolic pathways and dysregulated canonical circadian gene expressions. These findings support the idea that disrupting the circadian clock could provide an improved ALD mouse model for further applications, such as facilitating identification of potential therapeutic targets for the prevention and treatment of ALD.