Alcohol Consumption During Muscle Disuse Causes Differential Signaling Responses in a Muscle-Specific Manner in Mice

Excessive alcohol consumption promotes clinical myopathy and injury-related immobilization. Because both alcohol and disuse jeopardize muscle health, their combined effects may synergistically accelerate fiber type-dependent muscle wasting. Ten-week-old male C57BL/6J mice were fed a control or 5% alcohol-diet for 3 weeks (NIAAA-model), with or without 1 week of unilateral hindlimb immobilization, generating four sets of limb muscles (<i>n</i> = 9/grp): control (CO), with immobilization (CI), alcohol (AL), with immobilization (AI). Gastrocnemius and soleus muscles were atrophied by CI, AL, and AI, whereas quadriceps atrophy was induced by CI and AI only (all <i>p</i> < 0.05). In soleus, CI, AL, and AL decreased p-mTOR (~40-60%, <i>p</i> < 0.01) and p-p70S6K (~50-87%, <i>p</i> < 0.05), indicating suppressed anabolic signaling. In contrast, in the quadriceps, alcohol increased p-4EBP1 by ~200% (<i>p</i> < 0.01), while p-Akt was elevated by ~180%, only in AI (<i>p</i> < 0.01). Myogenesis signaling was inhibited by alcohol and immobilization. For protein degradation, immobilization increased MAFbx by >50% in both muscles (<i>p</i> < 0.01). Quadriceps exhibited increased p-PERK (+53%) under AI (<i>p</i> < 0.05), whereas several markers of ER stress were reduced by all interventions in soleus (<i>p</i> < 0.05). These findings suggest that alcohol consumption does not exacerbate immobilization-induced atrophy; however, alcohol suppresses anabolic signaling in soleus, suggesting greater susceptibility to myopathy.