Muscle follistatin gene delivery increases muscle protein synthesis independent of periodical physical inactivity and fasting
| Autor: | Tuuli A. Nissinen, Arja Pasternack, Juulia H. Lautaoja, Juha J. Hulmi, Vasco Fachada, Olli Ritvos, Jaakko Hentilä, Riikka Kivelä |
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| Přispěvatelé: | Medicum, Department of Physiology, Faculty of Medicine, University of Helsinki, Growth factor physiology, STEMM - Stem Cells and Metabolism Research Program, Kivelä Lab, Research Programs Unit |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Male
0301 basic medicine Follistatin Muscle Proteins physical activity lihakset Myostatin Biochemistry Mice 0302 clinical medicine Tibialis anterior muscle media_common 2. Zero hunger biology Chemistry activins Fasting Dependovirus Muscle atrophy Circadian Rhythm Muscular Atrophy myostatin medicine.symptom fyysinen aktiivisuus Biotechnology medicine.medical_specialty fasting media_common.quotation_subject Mechanistic Target of Rapamycin Complex 1 Gene delivery 03 medical and health sciences Physical Conditioning Animal Internal medicine Genetics medicine Animals Molecular Biology paasto PI3K/AKT/mTOR pathway solufysiologia Sarcolemma JNK Mitogen-Activated Protein Kinases mechanistic target of rapamycin protein Appetite Genetic Therapy Mice Inbred C57BL 030104 developmental biology Endocrinology biology.protein 1182 Biochemistry cell and molecular biology 3111 Biomedicine proteiinit Energy Metabolism lihassurkastumasairaudet 030217 neurology & neurosurgery |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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