Chronic Alcohol Ingestion Impairs Exercise Effects On Muscle Clock While Blunting Exercise-induced Adaptations

The skeletal muscle clock contributes to the regulation of skeletal muscle health and function. Mutations to the muscle clock result in decreased muscle mass and strength, altered mitochondrial health, and substrate metabolism in the muscle. Chronic alcohol (EtOH) ingestion disrupts components of the core molecular clock, alters mitochondrial function, and decreases muscle mass and strength. Exercise is a potent stimulator of the muscle clock, and exercise training promotes muscle and mitochondrial health. PURPOSE: In the current study, we examined the potential protective effects of scheduled, voluntary wheel running on alcohol-induced disruptions to the skeletal muscle clock and the effects of alcohol on exercise-induced muscle adaptations. METHODS: Female C57BL6 mice were randomly assigned to one of 4 groups: CON SED (n = 26), ETOH SED (n = 27), CON EX (n = 28), ETOH EX (n = 25). Exercise (EX) mice had running wheel access from ZT13-15, while sedentary mice (SED) remained in their home cage. All mice were fed either control (CON) or alcohol (ETOH)-containing liquid diet. Grip strength was measured before and after the interventions. After 6 weeks, muscle was collected every 4 hrs and RT-PCR, Western blotting, and citrate synthase activity assay were performed in gastrocnemius. RESULTS: Transcription of Bmal1, Per1, and Per2 was disrupted in ETOH SED vs. CON SED, while core clock mRNA expression was unaltered in ETOH EX compared to ETOH SED. CON EX phase shifted Bmal1 and Per1 mRNA compared to CON SED, but ETOH EX was not different from CON EX. Alcohol blunted the hypertrophic response to exercise in the gastrocnemius, plantaris, and soleus muscles, and blunted the exercise induced increase in forelimb grip strength. Citrate synthase activity was increased with exercise training in control and EtOH mice, while Complex III and Complex IV mitochondrial protein content was increased in all groups compared to CON SED. CONCLUSION: This data suggests that scheduled voluntary wheel running may be unable to protect the muscle clock against alcohol-induced disruption and that alcohol partially blunts skeletal muscle adaptations to exercise training.