IGF-1 attenuates hypoxia-induced atrophy but inhibits myoglobin expression in C2C12 skeletal muscle myotubes

Eva L. Peters, Sandra M. van der Linde, Ilse S.P. Vogel, Mohammad Haroon, Carla Offringa, Gerard M.J. de Wit, Pieter Koolwijk, Willem J. van der Laarse, Richard T. Jaspers*

*Corresponding author for this work

Research output: Contribution to JournalArticleAcademicpeer-review


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.

Original languageEnglish
Article number1889
JournalInternational Journal of Molecular Sciences
Issue number9
Publication statusPublished - 1 Sept 2017


Acknowledgments: Mohammad Haroon was funded by the European Commission through MOVE-AGE, an Erasmus Mundus Joint Doctorate program (2011-0015). The authors would like to thank Jeroen Kole and René J. P. Musters for excellent help with live cell imaging.

FundersFunder number
European Commission2011-0015


    • Anabolic signaling
    • C2C12
    • Fatty acid
    • Hypertrophy
    • Hypoxia
    • Mitochondrial biosynthesis
    • MTOR
    • Myogenic regulatory factors
    • Myoglobin
    • Succinate dehydrogenase
    • VEGF


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