IGF-1 Attenuates Hypoxia-Induced Atrophy but Inhibits Myoglobin Expression in C2C12 Skeletal Muscle Myotubes

• Published in: International journal of molecular sciences 2017-09, Vol.18 (9), p.1889
• Main Authors: Peters, Eva L, van der Linde, Sandra M, Vogel, Ilse S P, Haroon, Mohammad, Offringa, Carla, de Wit, Gerard M J, Koolwijk, Pieter, van der Laarse, Willem J, Jaspers, Richard T
• Format: Article
• Language: English
• Subjects: anabolic signaling; Animals; Atrophy; C2C12; fatty acid; Gene expression; Gene Expression Regulation - genetics; Humans; Hypertrophy; Hypoxia; Hypoxia - genetics; Hypoxia - pathology; Insulin; Insulin-like growth factor I; Insulin-Like Growth Factor I - genetics; Insulin-like growth factors; Lipids; Mice; Mitochondria; Mitochondria - genetics; Mitochondria - metabolism; mitochondrial biosynthesis; mTOR; Muscle contraction; Muscle Contraction - drug effects; Muscle Fibers, Skeletal - metabolism; Muscle Fibers, Skeletal - pathology; Muscle, Skeletal - metabolism; Muscle, Skeletal - pathology; Muscular Atrophy - genetics; Muscular Atrophy - pathology; Musculoskeletal system; Myogenic Regulatory Factors; myoglobin; Myoglobin - genetics; Myoglobin - metabolism; Myoglobins; Myotubes; Oxygen - metabolism; Protein biosynthesis; Protein synthesis; Rapamycin; Rodents; Signal Transduction - drug effects; Skeletal muscle; succinate dehydrogenase; Succinate Dehydrogenase - genetics; Testosterone Congeners - metabolism; TOR protein; TOR Serine-Threonine Kinases - genetics; Transcription; VEGF
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms18091889

Chronic hypoxia is associated with muscle wasting and decreased oxidative capacity. By contrast, training under hypoxia may enhance hypertrophy and increase oxidative capacity as well as oxygen transport to the mitochondria, by increasing myoglobin (Mb) expression. The latter may be a feasible strategy to prevent atrophy under hypoxia and enhance an eventual hypertrophic response to anabolic stimulation. Mb expression may be further enhanced by lipid supplementation. We investigated individual and combined effects of hypoxia, insulin-like growth factor (IGF)-1 and lipids, in mouse skeletal muscle C2C12 myotubes. Differentiated C2C12 myotubes were cultured for 24 h under 20%, 5% and 2% oxygen with or without IGF-1 and/or lipid treatment. In culture under 20% oxygen, IGF-1 induced 51% hypertrophy. Hypertrophy was only 32% under 5% and abrogated under 2% oxygen. This was not explained by changes in expression of genes involved in contractile protein synthesis or degradation, suggesting a reduced rate of translation rather than of transcription. Myoglobin mRNA expression increased by 75% under 5% O₂ but decreased by 50% upon IGF-1 treatment under 20% O₂, compared to control. Inhibition of mammalian target of rapamycin (mTOR) activation using rapamycin restored Mb mRNA expression to control levels. Lipid supplementation had no effect on Mb gene expression. Thus, IGF-1-induced anabolic signaling can be a strategy to improve muscle size under mild hypoxia, but lowers Mb gene expression.