A1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä
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-tekijät tai -toimittajat

Nissinen, Tuuli
Hentilä, Jaakko
Fachada, Vasco
Lautaoja, Juulia
Hulmi, Juha

Julkaisun tiedot

Julkaisun kaikki tekijät tai toimittajat: Nissinen, Tuuli A.; Hentilä, Jaakko; Fachada, Vasco; Lautaoja, Juulia H.; Pasternack, Arja; Ritvos, Olli; Kivelä, Riikka; Hulmi, Juha J.

Lehti tai sarja: FASEB Journal

ISSN: 0892-6638

eISSN: 1530-6860

Julkaisuvuosi: 2021

Ilmestymispäivä: 09.02.2021

Volyymi: 35

Lehden numero: 5

Artikkelinumero: e21387

Kustantaja: John Wiley & Sons

Julkaisumaa: Yhdysvallat (USA)

Julkaisun kieli: englanti

DOI: https://doi.org/10.1096/fj.202002008r

Julkaisun avoin saatavuus: Avoimesti saatavilla

Julkaisukanavan avoin saatavuus: Osittain avoin julkaisukanava

Julkaisu on rinnakkaistallennettu (JYX): https://jyx.jyu.fi/handle/123456789/74202

Tiivistelmä

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.

YSO-asiasanat: lihakset; lihassurkastumasairaudet; solufysiologia; proteiinit; fyysinen aktiivisuus; paasto

Vapaat asiasanat: activins; myostatin; mechanistic target of rapamycin protein; physical activity; fasting

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