The effects of voluntary binge-patterned ethanol ingestion and daily wheel running on signaling of muscle protein synthesis and degradation in female mice.

Abstract

Excessive ethanol ingestion can reduce skeletal muscle protein synthesis (MPS) through the disruption of signaling along the Akt-mTOR pathway and increase muscle protein degradation (MPD) through the Ubiquitin Proteasome Pathway (UPP) and autophagy. Identification of interventions that curb the disrupting effects of alcohol misuse on MPS and MPD are of central importance for the prevention of chronic health complications that arise from muscle loss. Physical activity is one potential strategy to combat the deleterious effects of alcohol on skeletal muscle. Therefore, the purpose of this study was to investigate the interaction between daily wheel running and binge-patterned ethanol consumption, through episodes of voluntary binge-patterned ethanol drinking, on signaling factors along the Akt-mTOR, Ubiquitin-Proteasome, and autophagy pathways. Adult female C57BL/6J mice received daily access to cages with or without running wheels for 2.5h/day for five weeks. During the final five days of the study, mice received 2-4h of daily access to sipper tubes containing water (n=14 sedentary; n=15 running) or 20% ethanol (n=14 sedentary; n=16 running) 30min after running wheel access, using the "Drinking in the Dark" (DID) model of binge-patterned ethanol consumption. Immediately after the final episode of DID, gastrocnemius muscle was extracted. Western blotting was performed to measure proteins along Akt-mTOR, Ubiquitin-Proteasome, and autophagy pathways, and PCR was used to assess mRNA expression of atrogenes. Ethanol access increased expression of MAFbx by 82% (p=0.048), but did not robustly influence Akt-mTOR or UPP signaling. Daily wheel access did not prevent alcohol-induced MAFbx expression; however, ethanol access decreased the phosphorylation of p70S6K by 45% in running mice (p=0.020). These results suggest that physical activity may be insufficient to prevent alcohol-induced changes to signaling factors along pathways involved in muscle loss. Instead, binge-patterned ethanol ingestion may impair the benefits of physical activity on factors involved in MPS.