Muscle follistatin gene delivery increases muscle protein synthesis independent of periodical physical inactivity and fasting

Blocking of myostatin and activins effectively counteracts muscle atrophy. However, the potential interaction with physical inactivity fasting in regulation protein synthesis is poorly understood. We used blockade by recombinant adeno-associated virus (rAAV)-mediated follistatin (FS288) overexpression mouse tibialis anterior muscle. To investigate effects on synthesis, muscles were collected 7 days after rAAV-injection nighttime or daytime representing high low levels activity feeding, respectively, overnight fasting, refeeding, ad libitum feeding. Muscle was increased FS288 independent time day feeding status. activation mTORC1 signaling attenuated fasting. also amount mTOR colocalized lysosomes, but did not alter their localization toward sarcolemma. This study shows that gene delivery increases largely diurnal fluctuations food intake status, overriding physiological signals. important for eg cachectic sarcopenic patients reduced appetite. The FS288-induced increase may be part driven