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dc.contributor.authorNissinen, Tuuli A.
dc.contributor.authorHentilä, Jaakko
dc.contributor.authorFachada, Vasco
dc.contributor.authorLautaoja, Juulia H.
dc.contributor.authorPasternack, Arja
dc.contributor.authorRitvos, Olli
dc.contributor.authorKivelä, Riikka
dc.contributor.authorHulmi, Juha J.
dc.date.accessioned2021-02-12T11:30:07Z
dc.date.available2021-02-12T11:30:07Z
dc.date.issued2021
dc.identifier.citationNissinen, 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. <i>FASEB Journal</i>, <i>35</i>(5), Article e21387. <a href="https://doi.org/10.1096/fj.202002008r" target="_blank">https://doi.org/10.1096/fj.202002008r</a>
dc.identifier.otherCONVID_51454240
dc.identifier.urihttps://jyx.jyu.fi/handle/123456789/74202
dc.description.abstractBlocking 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.en
dc.format.mimetypeapplication/pdf
dc.languageeng
dc.language.isoeng
dc.publisherJohn Wiley & Sons
dc.relation.ispartofseriesFASEB Journal
dc.rightsCC BY-NC 4.0
dc.subject.otheractivins
dc.subject.othermyostatin
dc.subject.othermechanistic target of rapamycin protein
dc.subject.otherphysical activity
dc.subject.otherfasting
dc.titleMuscle follistatin gene delivery increases muscle protein synthesis independent of periodical physical inactivity and fasting
dc.typearticle
dc.identifier.urnURN:NBN:fi:jyu-202102121630
dc.contributor.laitosLiikuntatieteellinen tiedekuntafi
dc.contributor.laitosFaculty of Sport and Health Sciencesen
dc.contributor.oppiaineLiikuntafysiologiafi
dc.contributor.oppiaineExercise Physiologyen
dc.type.urihttp://purl.org/eprint/type/JournalArticle
dc.description.reviewstatuspeerReviewed
dc.relation.issn0892-6638
dc.relation.numberinseries5
dc.relation.volume35
dc.type.versionpublishedVersion
dc.rights.copyright© 2021 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.
dc.rights.accesslevelopenAccessfi
dc.relation.grantnumber275922
dc.subject.ysopaasto
dc.subject.ysofyysinen aktiivisuus
dc.subject.ysolihakset
dc.subject.ysoproteiinit
dc.subject.ysosolufysiologia
dc.subject.ysolihassurkastumasairaudet
dc.format.contentfulltext
jyx.subject.urihttp://www.yso.fi/onto/yso/p9686
jyx.subject.urihttp://www.yso.fi/onto/yso/p23102
jyx.subject.urihttp://www.yso.fi/onto/yso/p2784
jyx.subject.urihttp://www.yso.fi/onto/yso/p4332
jyx.subject.urihttp://www.yso.fi/onto/yso/p25367
jyx.subject.urihttp://www.yso.fi/onto/yso/p15977
dc.rights.urlhttps://creativecommons.org/licenses/by-nc/4.0/
dc.relation.doi10.1096/fj.202002008r
dc.relation.funderSuomen Akatemiafi
dc.relation.funderAcademy of Finlanden
jyx.fundingprogramAkatemiatutkijan tehtävä, SAfi
jyx.fundingprogramResearch post as Academy Research Fellow, AoFen
jyx.fundinginformationThis 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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