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

Abstract

Binge and chronic alcohol intake impair skeletal muscle and liver circadian clocks. Scheduled exercise is suggested to protect against circadian misalignment, like that induced by alcohol. It was tested whether scheduled, voluntary daily wheel running would protect the gastrocnemius and liver clocks against alcohol-induced perturbations. Female C57BL6/Hsd mice were assigned to 1 of 4 groups: control-sedentary (CON SED, n = 26), control-exercise (CON EX, n = 28), alcohol-sedentary (ETOH SED, n = 27), or alcohol-exercise (ETOH EX, n = 25). Exercise mice were granted access to running wheels for 2 h/day (ZT13-15) while ETOH mice consumed alcohol-containing liquid diet for 6 weeks. Tissues were collected every 4 h starting at ZT12 from 4-5 mice/group and were used for RNA/cDNA/RT-PCR (gastrocnemius and liver) and Western blotting (gastrocnemius). A second cohort of mice were weaned off alcohol, given regular chow, and continued daily exercise (2 h/day) for ~2 weeks. Then, all mice (EX and SED) were given 24-h wheel access for 1 week to assess cyclic running behaviors during abstinence. While alcohol differentially disrupted muscle and liver clocks in sedentary mice, differences between exercised groups were minimized. BMAL1 protein expression increased in the nuclear-enriched fraction in the gastrocnemius of both exercise groups compared to both sedentary groups. In the second cohort, wheel running was increased in ETOH EX compared to ETOH SED in the dark cycle. In the light cycle, ETOH mice ran less than CON mice, and EX mice ran less than SED mice despite all mice receiving chow diet and no EtOH. Overall, scheduled wheel running partially offset the alcohol-induced perturbations in the muscle and liver clock while ETOH and EX both influenced the timing of subsequent activity after the dietary intervention ended.