Skeletal Muscle Wasting during Cancer Progression: Exploring the Therapeutic Role of Enhanced Aerobic Capacity

Abstract

The aim of this study was to test whether enhanced aerobic capacity would counteract cancer cachexia by attenuating skeletal muscle wasting. For doing that, we have standardized a new rat model of cancer cachexia by injecting Walker 256 tumor cells in bone marrow. Importantly, this model displayed anorexia, exacerbated oxidative stress, inflammation and skeletal muscle atrophy restricted to glycolytic fibers. Twelve days post tumor cells injection, rats showed severe aerobic exercise intolerance when compared to health control rats (~2 fold, p < 0.001). Importantly, we observed a correlation between changes in exercise tolerance and the survival rate (p = 0.01, r = 0.74), suggesting that aerobic exercise capacity is a strong predictor of early death. In order to improve oxidative metabolism, we then submitted tumor‐bearing rats to two different exercise training protocols: moderated‐intensity training (MIT) and high‐intensity interval training (HIIT). MIT and HIIT have increased exercise capacity toward control rat levels and improved survival (+21% and +31%, respectively). Importantly, both protocols have not changed tumor size or prevented glycolytic muscle fiber atrophy (p > 0.05). However, MIT and HIIT have enhanced oxidative metabolism evaluated by citrate synthase activity (+71% and +60%, respectively) and total glutathione levels (+44% and +30%, respectively) in plantaris skeletal muscle. Collectively, our results suggest that aerobic exercise training does not counteract cancer‐induced skeletal muscle atrophy, but mitigate oxidative metabolism impairment, increasing survival.Financial support: FAPESP (2014/03016‐8).