Chronic binge alcohol‐induced skeletal muscle wasting: Implications for satellite cell function

Abstract

Chronic alcohol abuse is associated with skeletal muscle (SKM) myopathy in 40–60% of alcohol abusers. Alcohol‐induced myopathies result from decreased muscle protein synthesis and possibly accelerated muscle proteolysis. The contribution of impaired muscle regenerative capacity is unknown. Muscle stem cells, satellite cells (SC), repair and regenerate muscle tissue. The impact of chronic binge alcohol (CBA) on SC function is unknown. We hypothesized that CBA alters SC phenotype impairing their repair and regeneration capacity. To test this hypothesis, SKM was isolated from macaques after 19 mo daily intragastric sucrose‐or alcohol‐administration. SC regenerative potential was assessed by RT‐qPCR analysis of myogenic transcription factor expression (PAX7, MEF2C, MYOD, MYF5, MYOG). CBA significantly decreased MYF5 expression, a key differentiation transcription factor. Additionally, using picrosirius red staining, we found evidence for SKM fibrosis in CBA animals. Collagen Type I, an extracellular matrix protein secreted during fibrosis, inhibits SC differentiation. These results suggest that CBA impairs SC differentiation potential directly though inhibition of differentiation transcription factor expression and indirectly through SKM fibrosis. We speculate this leads to impaired SKM repair and regeneration and thus, the ability to maintain muscle mass. Support: AA09803, AA11290