Early detection of skeletal muscle bioenergetic deficit by non invasive 31-phosphorus magnetic resonance spectroscopy in mice exposed to cigarette smoke

Skeletal muscle dysfunction is a common feature in COPD which is associated with intrinsic muscular abnormalities, but it is not known whether there is an easy way of predicting their presence in early stage of disease. Using a mouse model of cigarette smoke exposure, we tested the hypothesis that 31-phosphorus magnetic resonance spectroscopy allows us to early detect skeletal muscle bioenergetic deficit. We employed this technique to assess the rate of ATP synthesis, and characterized the concomitant mitochondrial dynamics patterns in skeletal. We specifically explored whether experimental COPD model may alter mitochondrial respiratory chain complexes in peripheral muscles. We evaluated citrate synthase (CtS) and cytochrome c oxidase (COX) enzyme activities in gastrocnemius of mice. We found that rate of muscle ATP synthesis was reduced in skeletal muscle of mice exposed to cigarette smoke. Furthermore, ATP synthesis rate was directly related to mitochondrial enzyme activity. Emphysematous mice showed a significant reduction in body weight gain and decreased activity of CtS/COX. Taken together, these data support the hypothesis that in early stage of lung disease we are able to detect a decreased skeletal muscle ATP synthesis, in part caused by low mitochondrial enzyme activity. These findings may prove relevant to predict the skeletal bioenergetic deficit presence in the early stage of the lung disease and thus be able to act preventively in the evolution of the disease, besides placing mitochondria as potential therapeutic target for the treatment of COPD comorbidities.