Muscle follistatin gene delivery increases muscle protein synthesis independent of periodical physical inactivity and fasting
Nissinen, T. A., Hentilä, J., Fachada, V., Lautaoja, J. H., Pasternack, A., Ritvos, O., Kivelä, R., & Hulmi, J. J. (2021). Muscle follistatin gene delivery increases muscle protein synthesis independent of periodical physical inactivity and fasting. FASEB Journal, 35(5), Article e21387. https://doi.org/10.1096/fj.202002008r
Published inFASEB Journal
© 2021 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.
Blocking of myostatin and activins effectively counteracts muscle atrophy. However, the potential interaction with physical inactivity and fasting in the regulation of muscle protein synthesis is poorly understood. We used blockade of myostatin and activins by recombinant adeno‐associated virus (rAAV)‐mediated follistatin (FS288) overexpression in mouse tibialis anterior muscle. To investigate the effects on muscle protein synthesis, muscles were collected 7 days after rAAV‐injection in the nighttime or in the daytime representing high and low levels of activity and feeding, respectively, or after overnight fasting, refeeding, or ad libitum feeding. Muscle protein synthesis was increased by FS288 independent of the time of the day or the feeding status. However, the activation of mTORC1 signaling by FS288 was attenuated in the daytime and by overnight fasting. FS288 also increased the amount of mTOR colocalized with lysosomes, but did not alter their localization toward the sarcolemma. This study shows that FS288 gene delivery increases muscle protein synthesis largely independent of diurnal fluctuations in physical activity and food intake or feeding status, overriding the physiological signals. This is important for eg cachectic and sarcopenic patients with reduced physical activity and appetite. The FS288‐induced increase in mTORC1 signaling and protein synthesis may be in part driven by increased amount of mTOR colocalized with lysosomes, but not by their localization toward sarcolemma. ...
PublisherJohn Wiley & Sons
ISSN Search the Publication Forum0892-6638
Publication in research information system
MetadataShow full item record
- Liikuntatieteiden tiedekunta 
Related funder(s)Academy of Finland
Funding program(s)Academy Research Fellow, AoF
Additional information about fundingThis work was supported by the Academy of Finland (grant No. 275922 (JJH) and 297245 (RK)), and the Ellen and Artturi Nyyssönen Foundation (TAN).
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