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Int J Mol Sci. 2017 Sep 1;18(9). pii: E1889. doi: 10.3390/ijms18091889.

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

Author information

1
Laboratory for Myology, Faculty of Behavioral and Movement Sciences, Department of Human Movement Sciences, Amsterdam Movement Sciences, Vrije Universiteit Amsterdam, De Boelelaan 1108, 1081 HZ Amsterdam, The Netherlands. el.peters@vumc.nl.
2
Laboratory for Myology, Faculty of Behavioral and Movement Sciences, Department of Human Movement Sciences, Amsterdam Movement Sciences, Vrije Universiteit Amsterdam, De Boelelaan 1108, 1081 HZ Amsterdam, The Netherlands. desandra@hotmail.com.
3
Laboratory for Myology, Faculty of Behavioral and Movement Sciences, Department of Human Movement Sciences, Amsterdam Movement Sciences, Vrije Universiteit Amsterdam, De Boelelaan 1108, 1081 HZ Amsterdam, The Netherlands. ilsevogel@gmail.com.
4
Laboratory for Myology, Faculty of Behavioral and Movement Sciences, Department of Human Movement Sciences, Amsterdam Movement Sciences, Vrije Universiteit Amsterdam, De Boelelaan 1108, 1081 HZ Amsterdam, The Netherlands. m.h.mohammadazam@vu.nl.
5
Laboratory for Myology, Faculty of Behavioral and Movement Sciences, Department of Human Movement Sciences, Amsterdam Movement Sciences, Vrije Universiteit Amsterdam, De Boelelaan 1108, 1081 HZ Amsterdam, The Netherlands. c.offringa@vu.nl.
6
Laboratory for Myology, Faculty of Behavioral and Movement Sciences, Department of Human Movement Sciences, Amsterdam Movement Sciences, Vrije Universiteit Amsterdam, De Boelelaan 1108, 1081 HZ Amsterdam, The Netherlands. g.m.j.de.wit@vu.nl.
7
Department of Physiology, Amsterdam Cardiovascular Sciences, VU University Medical Center, De Boelelaan 1108, 1081 HZ Amsterdam, The Netherlands. p.koolwijk@vumc.nl.
8
Department of Physiology, Amsterdam Cardiovascular Sciences, VU University Medical Center, De Boelelaan 1108, 1081 HZ Amsterdam, The Netherlands. wj.vanderlaarse@vumc.nl.
9
Laboratory for Myology, Faculty of Behavioral and Movement Sciences, Department of Human Movement Sciences, Amsterdam Movement Sciences, Vrije Universiteit Amsterdam, De Boelelaan 1108, 1081 HZ Amsterdam, The Netherlands. r.t.jaspers@vu.nl.

Abstract

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.

KEYWORDS:

C2C12; VEGF; anabolic signaling; fatty acid; hypertrophy; hypoxia; mTOR; mitochondrial biosynthesis; myogenic regulatory factors; myoglobin; succinate dehydrogenase

PMID:
28862673
PMCID:
PMC5618538
DOI:
10.3390/ijms18091889
[Indexed for MEDLINE]
Free PMC Article

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