Scheduled Exercise Partially Offsets Alcohol-Induced Clock Dysfunction in Skeletal Muscle and Liver of Female Mice

Area of Science:

• Chronobiology
• Skeletal Muscle Physiology
• Hepatology
• Alcohol-Induced Organ Damage

Background:

• Chronic and binge alcohol consumption disrupt circadian clocks in skeletal muscle and liver tissues.
• Circadian misalignment can exacerbate alcohol's negative effects on organ function.
• Scheduled exercise is a potential intervention to mitigate circadian disruption.

Purpose of the Study:

• To investigate whether scheduled voluntary wheel running protects gastrocnemius muscle and liver circadian clocks from alcohol-induced perturbations.
• To assess the impact of exercise on molecular clock components and behavioral activity patterns during and after alcohol exposure.

Main Methods:

• Female mice were assigned to control or alcohol-consuming groups, with or without daily wheel running access for 6 weeks.
• Gastrocnemius and liver tissues were collected at regular intervals for RNA/cDNA/RT-PCR and Western blotting analysis of clock gene expression (e.g., BMAL1).
• A second cohort underwent a withdrawal period with continued exercise, followed by 24-hour wheel access to assess activity patterns.

Main Results:

• Alcohol differentially disrupted muscle and liver clocks in sedentary mice, but these differences were minimized in exercised groups.
• BMAL1 protein expression in the gastrocnemius muscle was elevated in both exercise groups compared to sedentary groups.
• Post-intervention, alcohol-exposed mice showed altered running behavior, with exercised mice exhibiting increased dark cycle activity but reduced light cycle activity.

Conclusions:

• Scheduled voluntary wheel running partially offsets alcohol-induced perturbations in skeletal muscle and liver circadian clocks.
• Exercise influences the molecular clock and behavioral rhythms, suggesting a protective role against alcohol's chronobiotic effects.
• Both alcohol consumption and exercise impact the timing of activity patterns, even after the cessation of alcohol intake.