Genetic disruption of circadian organization promotes alcohol-induced hepatic steatosis.

<p>(<b>A</b>) Alcohol-fed <i>Clock^Δ19/Δ19</i> mutant mice (CA) had a significantly greater liver/body weight ratio than control-fed mutants (CD), with an overall significant effect of diet (p<0.01). **p<0.01, two-way ANOVA followed by <i>post-hoc</i> Tukey-Kramer Multiple-Comparison test. (<b>B</b>) Alcohol-fed <i>Clock^Δ19/Δ19</i> mutant mice (CA) exhibited significant steatosis compared to all other experimental groups, with a significant overall effect of genotype (p<0.001), diet (p<0.001), as well as a significant interaction (p<0.05). *p<0.05, **p<0.01; two-way ANOVA followed by <i>post-hoc</i> Tukey-Kramer Multiple-Comparison test. No between group differences were observed for histological assessment of lobular inflammation (<b>C</b>) or ballooning degeneration (<b>D</b>). Histological assessments were performed by a blinded gastrointestinal pathologist. Steatosis score was based on % hepatocyte involvement: 0 = <5%, 1 = 5–33%, 2 = 34–66%, 3 = >67%. Lobular inflammation score was based on the number of foci/200× field: 0 = none, 1 = 1, 2 = 2–4, 3 = >4. Ballooning degeneration score was based on the presence and frequency of ballooned cells: 0 = none, 1 = few, 2 = prominent/many.