Effect of chronic ethanol exposure on the liver of Clock-mutant mice

Takashi Kudo, Toru Tamagawa, Shigenobu Shibata*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)


In humans, chronic ethanol consumption leads to a characteristic set of changes to the metabolism of lipids in the liver that is referred to as an "alcoholic fatty liver (AFL)". In severe cases, these metabolic changes result in the enlargement and fibrillization of the liver and are considered risk factors for cirrhosis and liver cancer. Clock-mutant mice have been shown to display abnormal lipid metabolism and alcohol preferences. To further understand the potential interactions between ethanol consumption, lipid metabolism, and the circadian clock, we investigated the effect of chronic ethanol intake on the lipid metabolism of Clock-mutant mice. We found that ethanol treatment produced a number of changes in the liver of Clock-mutant mice without impacting the wild-type controls. First, we found that 8 weeks of exposure to ethanol in the drinking water increased the weight of the liver in Clock-mutant mice. Ethanol treatment also increased triglyceride content of liver in Clock-mutant and wild-type mice. This increase was larger in the mutant mice. Finally, ethanol treatment altered the expression of a number of genes related to lipid metabolism in the Clock-mutant mice. Interestingly, this treatment did not impact circadian clock gene expression in the liver of either genotype. Thus, ethanol produces a number of changes in the liver of Clock-mutant mice that are not seen in the wild-type mice. These changes are consistent with the possibility that disturbance of circadian rhythmicity associated with the Clock mutation could be a risk factor for the development of an alcoholic fatty liver.

Original languageEnglish
Article number4
JournalJournal of Circadian Rhythms
Publication statusPublished - 2009 Apr 1
Externally publishedYes

ASJC Scopus subject areas

  • Physiology
  • Endocrine and Autonomic Systems


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