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

Research output: Contribution to journalArticleAcademicpeer-review

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.

Original languageEnglish
Article number1889
JournalInternational Journal of Molecular Sciences
Volume18
Issue number9
DOIs
Publication statusPublished - 1 Sep 2017

Cite this

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. / IGF-1 attenuates hypoxia-induced atrophy but inhibits myoglobin expression in C2C12 skeletal muscle myotubes. In: International Journal of Molecular Sciences. 2017 ; Vol. 18, No. 9.
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title = "IGF-1 attenuates hypoxia-induced atrophy but inhibits myoglobin expression in C2C12 skeletal muscle myotubes",
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 = "Anabolic signaling, C2C12, Fatty acid, Hypertrophy, Hypoxia, Mitochondrial biosynthesis, MTOR, Myogenic regulatory factors, Myoglobin, Succinate dehydrogenase, VEGF",
author = "Peters, {Eva L.} and {van der Linde}, {Sandra M.} and Vogel, {Ilse S.P.} and Mohammad Haroon and Carla Offringa and {de Wit}, {Gerard M.J.} and Pieter Koolwijk and {van der Laarse}, {Willem J.} and Jaspers, {Richard T.}",
year = "2017",
month = "9",
day = "1",
doi = "10.3390/ijms18091889",
language = "English",
volume = "18",
journal = "International Journal of Molecular Sciences",
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number = "9",

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

In: International Journal of Molecular Sciences, Vol. 18, No. 9, 1889, 01.09.2017.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - IGF-1 attenuates hypoxia-induced atrophy but inhibits myoglobin expression in C2C12 skeletal muscle myotubes

AU - Peters, Eva L.

AU - van der Linde, Sandra M.

AU - Vogel, Ilse S.P.

AU - Haroon, Mohammad

AU - Offringa, Carla

AU - de Wit, Gerard M.J.

AU - Koolwijk, Pieter

AU - van der Laarse, Willem J.

AU - Jaspers, Richard T.

PY - 2017/9/1

Y1 - 2017/9/1

N2 - 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.

AB - 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.

KW - Anabolic signaling

KW - C2C12

KW - Fatty acid

KW - Hypertrophy

KW - Hypoxia

KW - Mitochondrial biosynthesis

KW - MTOR

KW - Myogenic regulatory factors

KW - Myoglobin

KW - Succinate dehydrogenase

KW - VEGF

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U2 - 10.3390/ijms18091889

DO - 10.3390/ijms18091889

M3 - Article

VL - 18

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

SN - 1422-0067

IS - 9

M1 - 1889

ER -