Conditional Activation of Akt in Adult Skeletal Muscle Induces Rapid Hypertrophy
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Skeletal muscle atrophy is a severe morbidity caused by a variety of conditions, including cachexia, cancer, AIDS, prolonged bedrest, and diabetes. One strategy in the treatment of atrophy is to induce the pathways normally leading to skeletal muscle hypertrophy. The pathways that are sufficient to induce hypertrophy in skeletal muscle have been the subject of some controversy. We describe here the use of a novel method to produce a transgenic mouse in which a constitutively active form of Akt can be inducibly expressed in adult skeletal muscle and thereby demonstrate that acute activation of Akt is sufficient to induce rapid and significant skeletal muscle hypertrophy in vivo, accompanied by activation of the downstream Akt/p70S6 kinase protein synthesis pathway. Upon induction of Akt in skeletal muscle, there was also a significant decrease in adipose tissue. These findings suggest that pharmacologic approaches directed toward activating Akt will be useful in inducing skeletal muscle hypertrophy and that an increase in lean muscle mass is sufficient to decrease fat storage.
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In animal models, mTORC1 activation by animal-specific resistance training, IGF-1, or Akt1 expression causes muscle hypertrophy.
“In animal models, mTORC1 activation either by animal-specific resistance training, IGF-1 [36], or Akt1 expression [37] causes muscle hypertrophy.”
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 [37]
Activation of Akt in skeletal muscle leads to rapid muscle hypertrophy accompanied by improved metabolism.
“Activation of Akt in skeletal muscle leads to rapid muscle hypertrophy 37 accompanied by improved metabolism 38.”
From Akt-dependent anabolic activity of natural and synthetic brassinosteroids in rat skeletal muscle cells (2011) · cites this paper as [37]
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- Authors
- Lai, K.-M. V., Gonzalez, M., Poueymirou, W. T., Kline, W. O., Na, E., Zlotchenko, E., Stitt, T. N., Economides, A. N., Yancopoulos, G. D., & Glass, D. J.
- Affiliations
- Regeneron (United States) (US)
- Corresponding author
- Glass, David J.
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 2004-11-01
- Volume
- 24
- Issue
- 21
- Pages
- 9295-9304
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- PMC
- PMC522257
- OpenAlex
- W2148625376
- Cited by
- 442
- References
- 25
- Citations by year
- 2026: 6 · 2025: 5 · 2024: 16 · 2023: 17 · 2022: 21 · 2021: 17 · 2020: 17 · 2019: 21 · 2018: 18 · 2017: 10 · 2016: 21 · 2015: 23 · 2014: 25 · 2013: 34 · 2012: 22
- FWCI
- 7.34
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Molecular and Cellular Biology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Procter and Gamble
- Regeneron Pharmaceuticals
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Muscle metabolism and nutrition
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- Akt, skeletal muscle hypertrophy, skeletal muscle atrophy, p70 S6 kinase, protein synthesis, transgenic mice, adipose tissue, lean muscle mass, cachexia, Akt activation
- MeSH terms
- Adipose Tissue, Aging, Animals, Enzyme Activation, Female, Hypertrophy, Male, Mice, Inbred C57BL, Mice, Transgenic, Microscopy, Fluorescence, Proto-Oncogene Proteins, Tamoxifen, Protein Serine-Threonine Kinases, Muscle, Skeletal, Microscopy, Confocal, Proto-Oncogene Proteins c-akt, Mice
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