Cancer cachexia is a multifactorial and devastating
syndrome characterized by severe
skeletal muscle mass loss and dysfunction. As
cachexia still has neither a
cure nor an effective
treatment , better
understanding of
skeletal muscle plasticity in the context of
cancer is of great importance. Although
aerobic exercise training (
AET ) has been shown as an important complementary
therapy for
chronic diseases and associated comorbidities, the impact of
AET on
skeletal muscle mass
maintenance during
cancer progression has not been well documented yet. Here, we show that previous
AET induced a protective mechanism against
tumor -induced
muscle wasting by modulating the Akt/
mTORC1 signaling and
eukaryotic initiation factors , specifically
eIF2 -α. Thereafter, it was determined whether the in vivo Akt activation would induce a hypertrophic profile in cachectic
muscles . As observed for the first
time , Akt-induced
hypertrophy was able and sufficient to either prevent or revert
cancer cachexia by modulating both Akt/
mTORC1 pathway and the
eIF-2 α activation, and induced a better
muscle functionality. These findings provide evidence that
skeletal muscle tissue still preserves hypertrophic potential to be stimulated by either
AET or
gene therapy to counteract
cancer cachexia .