A1 Journal article (refereed)
Muscle follistatin gene delivery increases muscle protein synthesis independent of periodical physical inactivity and fasting (2021)
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
JYU authors or editors
Publication details
All authors or editors: Nissinen, Tuuli A.; Hentilä, Jaakko; Fachada, Vasco; Lautaoja, Juulia H.; Pasternack, Arja; Ritvos, Olli; Kivelä, Riikka; Hulmi, Juha J.
Journal or series: FASEB Journal
ISSN: 0892-6638
eISSN: 1530-6860
Publication year: 2021
Publication date: 09/02/2021
Volume: 35
Issue number: 5
Article number: e21387
Publisher: John Wiley & Sons
Publication country: United States
Publication language: English
DOI: https://doi.org/10.1096/fj.202002008r
Publication open access: Openly available
Publication channel open access: Partially open access channel
Publication is parallel published (JYX): https://jyx.jyu.fi/handle/123456789/74202
Abstract
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.
Keywords: muscles; muscular atrophies; cell physiology; proteins; physical activeness; fasting
Free keywords: activins; myostatin; mechanistic target of rapamycin protein; physical activity; fasting
Contributing organizations
Related projects
- Riittävä lihasmassa ja aerobinen kunto eliniän pidentäjinä lihaskadossa
- Hulmi, Juha
- Academy of Finland
Ministry reporting: Yes
Reporting Year: 2021
Preliminary JUFO rating: 2