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

Area of Science:

• Muscle physiology
• Alcohol-induced myopathy
• Disuse atrophy

Background:

• Excessive alcohol consumption and muscle disuse (immobilization) are known to negatively impact muscle health.
• The combined effects of alcohol and disuse on muscle wasting, particularly fiber type-dependent atrophy, require further investigation.

Purpose of the Study:

• To investigate the independent and combined effects of alcohol consumption and hindlimb immobilization on muscle mass and signaling pathways in mice.
• To determine if alcohol exacerbates immobilization-induced muscle atrophy and to identify underlying molecular mechanisms.

Main Methods:

• Male C57BL/6J mice were subjected to a control diet or a 5% alcohol diet for 3 weeks, with or without 1 week of unilateral hindlimb immobilization.
• Muscle mass changes and key signaling proteins involved in anabolic and catabolic pathways (e.g., mTOR, Akt, MAFbx) were analyzed in gastrocnemius, soleus, and quadriceps muscles.

Main Results:

• Both immobilization and alcohol consumption induced atrophy in the soleus muscle, while only immobilization and combined alcohol-plus-immobilization caused quadriceps atrophy.
• Alcohol suppressed anabolic signaling (p-mTOR, p-p70S6K) in the soleus muscle, whereas it increased pro-myogenic signaling markers (p-4EBP1, p-Akt) in the quadriceps under immobilization.
• Immobilization increased the expression of the ubiquitin ligase MAFbx, a marker of protein degradation, in both muscles.

Conclusions:

• Alcohol consumption alone suppresses anabolic signaling in the soleus muscle, suggesting a predisposition to myopathy.
• Alcohol does not appear to exacerbate immobilization-induced muscle atrophy, but it significantly alters molecular signaling pathways in a muscle-specific manner.