Sedentary lifestyle induces oxidative stress and atrophy in rat skeletal muscle

Abundant evidence indicates that skeletal muscle is an important endocrine organ that plays a key role in regulating metabolic homeostasis. Therefore, maintaining healthy skeletal muscles is essential to good health. While it is established that prolonged skeletal muscle inactivity results in both oxidative stress and muscle atrophy, it remains unknown if the change from an active to a sedentary lifestyle promotes a similar increase in oxidative stress and locomotor muscle atrophy. We tested the hypothesis that the transition from active to sedentary living results in the rapid development of oxidative damage and fiber atrophy in locomotor skeletal muscles. Adult Wistar rats were randomly divided into control (CON; n=8) and sedentary (SED; n=8) groups. During a seven-day experimental period, animals in the CON group were housed in standard size cages permitting free movement, while animals in the SED group were housed in small cages that promoted sedentary behavior. At the end of the experimental protocol, soleus muscles were removed and the activities of antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX) were determined along with two biomarkers of muscle oxidative stress (i.e., levels of advanced protein oxidation (AOPP) and 4-hydroxynonenal (4-HNE)). Living in the reduced-size cage resulted in muscle atrophy as evidenced by a 17.2% decrease in the soleus to body weight ratio ( P<0 . 001 ). Moreover, the activities of SOD, CAT and GPX in the soleus muscle were significantly decreased in SED animals compared to CON ( P <0.05). Finally, compared to CON, sedentary living increased both AOPP and 4-HNE levels in muscles of SED animals ( P <0.001 and P <0.05, respectively). These findings provide the first evidence that the transition from an active to sedentary lifestyle results in the rapid onset of oxidative stress and atrophy in locomotor skeletal muscles. Importantly, these results suggest that an impaired antioxidant defense contributes to sedentary behavior-induced oxidative stress in locomotor muscles.