Important role for AMPKαl in limiting skeletal muscle cell hypertrophy
Open accessAbstract
Activation of AMP‐activated protein kinase (AMPK) inhibits protein synthesis through the suppression of the mammalian target of rapamycin complex 1 (mTORCl), a critical regulator of muscle growth. The purpose of this investigation was to determine the role of the AMPKα1 catalytic subunit on muscle cell size control and adaptation to muscle hypertrophy. We found that AMPKα1(—/—) primary cultured myotubes and myofibers exhibit larger cell size compared with control cells in response to chronic Akt activation. We next subjected the plantaris muscle of AMPKα1(—/—) and control mice to mechanical overloading to induce muscle hypertrophy. We observed significant elevations of AMPKαl activity in the control muscle at days 7 and 21 after the overload. Overloading‐induced muscle hypertrophy was significantly accelerated in AMPKα1(—/—) mice than in control mice [+32 vs . +53% at day 7 and +57 vs . +76% at day 21 in control vs . AMPKα1(—/—) mice, respectively]. This enhanced growth of AMPKα1‐deficient muscle was accompanied by increased phosphorylation of mTOR signaling downstream targets and decreased phosphorylation of eukaryotic elongation factor 2. These results demonstrate that AMPKα1 plays an important role in limiting skeletal muscle overgrowth during hypertrophy through inhibition of the mTOR‐signaling pathway.—Mounier, R., Louise Lantier, Leclerc, J., Sotiropoulos, A., Pende, M., Daegelen, D., Sakamoto, K., Foretz, M., Viollet, B. Important role for AMPKa1 in limiting skeletal muscle cell hypertrophy. FASEBJ. 23, 2264–2273 (2009)
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Mice in which the α1 isoform of AMPK was knocked out showed a 33% greater increase in muscle fiber size and enhanced mTOR signaling to S6K and 4E-BP1 in response to training than wild-type mice.
“Consistent with the hypothesis that α1-AMPK limited growth, mice in which the α1 isoform of AMPK was knocked out showed a 33 % greater increase in muscle fiber size and enhanced mTOR signaling to S6K and 4E-BP1 in response to training than wild-type mice [49].”
From Using Molecular Biology to Maximize Concurrent Training (2014) · cites this paper as [49]
The α1-AMPK knockout mice showed significantly greater α2-AMPK activity in an effort to compensate for the loss of α1, but this was unable to restrict growth.
“It is important to note that the α1-AMPK knockout mice showed significantly greater α2-AMPK activity in an effort to compensate for the loss of α1, but this was unable to restrict growth.”
From Using Molecular Biology to Maximize Concurrent Training (2014) · cites this paper as [49]
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“Consistent with the hypothesis that a1-AMPK limited growth, mice in which the a1 isoform of AMPK was knocked out showed a 33 % greater increase in muscle fiber size and enhanced mTOR signaling to S6K and 4E-BP1 in response to training than wild-type mice [49].”
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- Authors
- Mounier, R., Lantier, L., Leclerc, J., Sotiropoulos, A., Pende, M., Daegelen, D., Sakamoto, K., Foretz, M., & Viollet, B.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Inserm (FR)
- University of Dundee (GB)
- Institut Cochin Université Paris Descartes CNRS (UMR 8104) Paris France
- Venue
- The FASEB Journal
- Publisher
- Wiley
- Published
- 2009-02-23
- Volume
- 23
- Issue
- 7
- Pages
- 2264-2273
- ISSN
- 0892-6638 (ISSN-L)
- 1530-6860
- OpenAlex
- W1982450147
- Cited by
- 133
- References
- 49
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 5 · 2023: 5 · 2022: 2 · 2021: 6 · 2020: 4 · 2019: 3 · 2018: 15 · 2017: 13 · 2016: 6 · 2015: 9 · 2014: 9 · 2013: 17 · 2012: 15
- FWCI
- 4.42
- Type
- journal article
- Language
- en
- Open access
- green
- inserm.hal.science
- Licence
- Locations
- The FASEB Journal (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion, other-oa)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Funders
- Agence Nationale de la Recherche (ANR-06-PHYS-0026)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Muscle metabolism and nutrition
- Keywords
- AMPKα1, AMPK, skeletal muscle hypertrophy, mTOR signaling, mTORC1, Akt signaling, muscle growth regulation, mechanical overload, plantaris muscle, elongation factor 2
- MeSH terms
- Animals, Carrier Proteins, Hypertrophy, Phosphorylation, Stress, Mechanical, Signal Transduction, Phosphotransferases (Alcohol Group Acceptor), Mice, Knockout, Muscle, Skeletal, Protective Agents, Peptide Elongation Factor 2, Cell Enlargement, Proto-Oncogene Proteins c-akt, Mice, AMP-Activated Protein Kinases, TOR Serine-Threonine Kinases
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