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
Publication in research information system
MetadataShow full item record
- Liikuntatieteiden tiedekunta 
Related funder(s)Academy of Finland
Funding program(s)Research post as 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).
Showing items with similar title or keywords.
Activin Receptor Ligand Blocking and Cancer Have Distinct Effects on Protein and Redox Homeostasis in Skeletal Muscle and Liver Hentilä, Jaakko; Nissinen, Tuuli; Korkmaz, Ayhan; Lensu, Sanna; Silvennoinen, Mika; Pasternack, Arja; Ritvos, Olli; Atalay, Mustafa; Hulmi, Juha (Frontiers Research Foundation, 2019)Muscle wasting in cancer cachexia can be alleviated by blocking activin receptor type 2 (ACVR2) ligands through changes in protein synthesis/degradation. These changes in cellular and protein metabolism may alter protein ...
Targeting the Activin Receptor Signaling to Counteract the Multi-Systemic Complications of Cancer and Its Treatments Hulmi, Juha J.; Nissinen, Tuuli A.; Penna, Fabio; Bonetto, Andrea (MDPI, 2021)Muscle wasting, i.e., cachexia, frequently occurs in cancer and associates with poor prognosis and increased morbidity and mortality. Anticancer treatments have also been shown to contribute to sustainment or exacerbation ...
Muscle and serum metabolomes are dysregulated in colon-26 tumor-bearing mice despite amelioration of cachexia with activin receptor type 2B ligand blockade Lautaoja, Juulia; Lalowski, Maciej; Nissinen, Tuuli; Hentilä, Jaakko; Shi, Yi; Ritvos, Olli; Cheng, Sulin; Hulmi, Juha (American Physiological Society, 2019)Cancer-associated cachexia reduces survival, which has been attenuated by blocking the activin receptor type 2B (ACVR2B) ligands in mice. The purpose of this study was to unravel the underlying physiology and novel cachexia ...
Molecular and physiological effects of muscle wasting and its treatment by blocking myostatin and activins Nissinen, Tuuli (2020)Muscle wasting, occurring e.g. in cancer, is associated with poor prognosis, and cancer treatments may even exacerbate the wasting. The prevention of muscle wasting has improved survival in preclinical cancer models, but ...
Blocking Activin Receptor Ligands Is Not Sufficient to Rescue Cancer-Associated Gut Microbiota : A Role for Gut Microbial Flagellin in Colorectal Cancer and Cachexia? Pekkala, Satu; Keskitalo, Anniina; Kettunen, Emilia; Lensu, Sanna; Nykänen, Noora; Kuopio, Teijo; Ritvos, Olli; Hentilä, Jaakko; Nissinen, Tuuli A.; Hulmi, Juha J. (MDPI AG, 2019)Colorectal cancer (CRC) and cachexia are associated with the gut microbiota and microbial surface molecules. We characterized the CRC-associated microbiota and investigated whether cachexia affects the microbiota composition. ...