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

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

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Ministry reporting: Yes

Reporting Year: 2021

Preliminary JUFO rating: 2