Myotube growth is associated with cancer-like metabolic reprogramming and is limited by phosphoglycerate dehydrogenase
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The Warburg effect links growth and glycolysis in cancer. A key purpose of the Warburg effect is to generate glycolytic intermediates for anabolic reactions, such as nucleotides → RNA/DNA and amino acids → protein synthesis. The aim of this study was to investigate whether a similar ‘glycolysis-for-anabolism’ metabolic reprogramming also occurs in hypertrophying muscles. To interrogate this, we first induced C2C12 myotube hypertrophy with IGF-1. We then added 14C glucose to the differentiation medium and measured radioactivity in isolated protein and RNA to establish whether 14C had entered anabolism. We found that especially protein became radioactive, suggesting a glucose → glycolytic intermediates → non-essential amino acid(s) → protein series of reactions, the rate of which was increased by IGF-1. Next, to investigate the importance of glycolytic flux and non-essential amino acid synthesis for myotube hypertrophy, we exposed C2C12 and primary mouse myotubes to the glycolysis inhibitor 2-Deoxy-d-glucose (2DG). We found that inhibiting glycolysis lowered C2C12 and primary myotube size. Similarly, siRNA silencing of PHGDH, the key enzyme of the serine biosynthesis pathway, decreased C2C12 and primary myotube size; whereas retroviral PHGDH overexpression increased C2C12 myotube size. Together these results suggest that glycolysis is important for hypertrophying myotubes, which reprogram their metabolism to facilitate anabolism, similar to cancer cells.
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14C from 14C glucose ends up in protein, and stimulating protein synthesis increases the rate at which this occurs.
“Furthermore, we and others have found that the 14C from 14C glucose ends up in protein, and that stimulating protein synthesis increases the rate at which this occurs [178].”
From Effects of Skeletal Muscle Hypertrophy on Fat Mass and Glucose Homeostasis in Humans and Animals: A Narrative Review with Systematic Literature Search (2025) · cites this paper as [178]
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Self-citation
- Authors
- Stadhouders, L. E. M., Smith, J. A. B., Gabriel, B. M., Verbrugge, S. A. J., Hammersen, T. D., Kolijn, D., Vogel, I. S. P., Mohamed, A. D., de Wit, G. M. J., Offringa, C., Hoogaars, W. M. H., Gehlert, S., Wackerhage, H., & Jaspers, R. T.
- Affiliations
- Amsterdam Movement Sciences (NL)
- University of Aberdeen (GB)
- Technical University of Munich (DE)
- Institute of Cancer Research (GB)
- German Sport University Cologne (DE)
- Corresponding author
- Jaspers, Richard T.
- ORCID
- Venue
- Experimental Cell Research
- Publisher
- Elsevier BV
- Published
- 2023-12
- Volume
- 433
- Issue
- 2
- Pages
- 113820
- ISSN
- 0014-4827 (ISSN-L)
- OpenAlex
- W4387881480
- Cited by
- 19
- References
- 65
- Citations by year
- 2026: 5 · 2025: 4 · 2024: 6 · 2023: 2 · 2022: 1 · 2021: 1
- FWCI
- 1.51
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Experimental Cell Research (publishedVersion, cc-by)
- PubMed (publishedVersion)
- VU Research Portal (publishedVersion, other-oa)
- Aberdeen University Research Archive (Aberdeen University) (submittedVersion)
- mediaTUM – the media and publications repository of the Technical University Munich (Technical University Munich) (submittedVersion)
- Funders
- Sarcoma UK (SUK09.2015)
- Wenner-Gren Foundation
- Cancer Research UK
- European Foundation for the Study of Diabetes
- Novo Nordisk Fonden (NNF19OC0055072)
- Biochemical Society
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- myotube hypertrophy, metabolic reprogramming, Warburg effect, glycolysis, PHGDH, serine biosynthesis, insulin-like growth factor I, 2-deoxyglucose, C2C12 myotubes, muscle growth
- MeSH terms
- Amino Acids, Animals, Glucose, Hypertrophy, Insulin-Like Growth Factor I, Neoplasms, RNA, Muscle Fibers, Skeletal, Phosphoglycerate Dehydrogenase, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
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