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Conditional Activation of Akt in Adult Skeletal Muscle Induces Rapid Hypertrophy
Open accessAbstract
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 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]
In the citing paper
“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]
Citations
Cites
The phosphatidylinositol 3-Kinase–AKT pathway in human cancer
Vivanco, I., & Sawyers, C. L. (2002) · Nature reviews. Cancer · doi:10.1038/nrc839 · Cited by 6,155
Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B
Cross, D. A. E., Alessi, D. R., Cohen, P., Andjelkovich, M., & Hemmings, B. A. (1995) · Nature · doi:10.1038/378785a0 · Cited by 5,244
Cellular survival: a play in three Akts
Datta, S. R., Brunet, A., & Greenberg, M. E. (1999) · Genes & Development · doi:10.1101/gad.13.22.2905 · Cited by 4,216
Identification of ubiquitin ligases required for skeletal muscle atrophy.
Bodine, S. C., Latres, E., Baumhueter, S., Lai, V. K.-M., Nunez, L., Clarke, B. A., Poueymirou, W. T., Panaro, F. J., Na, E., Dharmarajan, K., et al. (2001) · Science · doi:10.1126/science.1065874 · Cited by 3,521
Self-citationBodine, S. C., Stitt, T. N., Gonzalez, M., Kline, W. O., Stover, G. L., Bauerlein, R., Zlotchenko, E., Scrimgeour, A., Lawrence, J. C., Glass, D. J., et al. (2001) · Nature Cell Biology · doi:10.1038/ncb1101-1014 · Cited by 2,752
Self-citationA Calcineurin-Dependent Transcriptional Pathway for Cardiac Hypertrophy
Molkentin, J. D., Lu, J., Antos, C. L., Markham, B. E., Richardson, J. A., Robbins, J. M., Grant, S. R., & Olson, E. N. (1998) · Cell · doi:10.1016/s0092-8674(00)81573-1 · Cited by 2,566
Rommel, C., Bodine, S. C., Clarke, B. A., Rossman, R., Nunez, L., Stitt, T. N., Yancopoulos, G. D., & Glass, D. J. (2001) · Nature Cell Biology · doi:10.1038/ncb1101-1009 · Cited by 1,583
Self-citationGrowth Hormone and the Insulin-Like Growth Factor System in Myogenesis*
Florini, J. R., Ewton, D. Z., & Coolican, S. A. (1996) · Endocrine Reviews · doi:10.1210/edrv-17-5-481 · Cited by 1,148
Musarò, A., McCullagh, K., Paul, A., Houghton, L., Dobrowolny, G., Molinaro, M., Barton, E. R., L Sweeney, H., & Rosenthal, N. (2001) · Nature Genetics · doi:10.1038/84839 · Cited by 1,137 · cited 1×
“When IGF-1 levels were enhanced by using a musclespecific promoter in transgenic mice, increased muscle size resulted (4, 13).”
BackgroundRegulation of Cre Recombinase Activity by Mutated Estrogen Receptor Ligand-Binding Domains
Feil, R., Wagner, J. D., METZGER, D., & Chambon, P. (1997) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1997.7124 · Cited by 992
Growth retardation and increased apoptosis in mice with homozygous disruption of the akt1 genePreprint
Chen, W. S., Xu, P.-Z., Gottlob, K., Chen, M.-L., Sokol, K. A., Shiyanova, T., Roninson, I. B., Weng, W., Suzuki, R., Tobe, K., et al. (2001) · Genes & Development · doi:10.1101/gad.913901 · Cited by 941
NAVÉ, B. T., Ouwens, D. M., Withers, D. J., Alessi, D. R., & Shepherd, P. R. (1999) · Biochemical Journal · doi:10.1042/bj3440427 · Cited by 926
Zambrowicz, B., Imamoto, A., Fiering, S., Herzenberg, L. A., Kerr, W. G., & Soriano, P. M. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.8.3789 · Cited by 850
Peng, X.-D., Xu, P.-Z., Chen, M.-L., Hahn-Windgassen, A., Skeen, J. E., Jacobs, J., Sundararajan, D., Chen, W. S., Crawford, S. E., Coleman, K. G., et al. (2003) · Genes & Development · doi:10.1101/gad.1089403 · Cited by 836
Differentiation Stage-Specific Inhibition of the Raf-MEK-ERK Pathway by Akt
Rommel, C., Clarke, B. A., Zimmermann, S., Nuñez, L., Rossman, R., Reid, K., Moelling, K., Yancopoulos, G. D., & Glass, D. J. (1999) · Science · doi:10.1126/science.286.5445.1738 · Cited by 760
Self-citationSignalling pathways that mediate skeletal muscle hypertrophy and atrophy
Glass, D. J. (2003) · Nature Cell Biology · doi:10.1038/ncb0203-87 · Cited by 694
Self-citationColeman, M. E., DeMayo, F., Yin, K. C., Lee, H. M., Geske, R., Montgomery, C., & Schwartz, R. J. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.20.12109 · Cited by 642
High-throughput engineering of the mouse genome coupled with high-resolution expression analysis
Valenzuela, D. M., Murphy, A. J., Frendewey, D. A., Gale, N. W., Economides, A. N., Auerbach, W., Poueymirou, W. T., Adams, N. C., Rojas, J., Yasenchak, J., et al. (2003) · Nature Biotechnology · doi:10.1038/nbt822 · Cited by 583
Self-citationAkt/Protein Kinase B Promotes Organ Growth in Transgenic Mice
Shioi, T., McMullen, J. R., Kang, P. M., Douglas, P. S., Obata, T., Franke, T. F., Cantley, L. C., & Izumo, S. (2002) · Molecular and Cellular Biology · doi:10.1128/mcb.22.8.2799-2809.2002 · Cited by 503
Stimulation of Slow Skeletal Muscle Fiber Gene Expression by Calcineurin in Vivo
Naya, F. J., Mercer, B. M., Shelton, J. M., Richardson, J. A., Williams, R. S., & Olson, E. N. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.7.4545 · Cited by 420
Pallafacchina, G., Calabria, E., Serrano, A. L., Kalhovde, J. M., & Schiaffino, S. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.142166599 · Cited by 402
Activation of insulin-like growth factor gene expression during work-induced skeletal muscle growth
DeVol, D. L., Rotwein, P. S., Sadow, J. L., NOVAKOFSKI, J. E., & Bechtel, P. J. (1990) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1990.259.1.e89 · Cited by 329
Goldspink, D. F., Garlick, P. J., & McNurlan, M. A. (1983) · Biochemical Journal · doi:10.1042/bj2100089 · Cited by 146
Attenuation of Mammalian Target of Rapamycin Activity by Increased cAMP in 3T3-L1 Adipocytes
Scott, P., & Lawrence, J. C. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.51.34496 · Cited by 90
Ralston, E., & Ploug, T. (1996) · PubMed · Cited by 12
Research works printed but not linked: 4
- DeVol D. L., 1990, Am. J. Physiol., 259, E89
- Florini J. R., 1996, Endocrinol. Rev., 17, 481
- Pallafacchina G., 2002, Proc. Natl. Acad. Sci. USA, 25, 25
- Ralston E., 1996, Scanning Microsc. Suppl., 10, 249
Cited by
Sorted by citations
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Schiaffino, S., Dyar, K. A., Ciciliot, S., Blaauw, B., & Sandri, M. (2013) · The FEBS Journal · doi:10.1111/febs.12253 · Cited by 1,492
Cellular and molecular mechanisms of muscle atrophy
Bonaldo, P., & Sandri, M. (2013) · Disease Models & Mechanisms · doi:10.1242/dmm.010389 · Cited by 1,284
Cancer Cachexia: Mediators, Signaling, and Metabolic Pathways
Fearon, K. C. H., Glass, D. J., & Guttridge, D. C. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.06.011 · Cited by 1,244
Self-citationTisdale, M. J. (2009) · Physiological Reviews · doi:10.1152/physrev.00016.2008 · Cited by 1,216
The Human Obesity Gene Map: The 2005 Update
Rankinen, T., Zuberi, A., Chagnon, Y. C., Weisnagel, S. J., Argyropoulos, G., Walts, B., Pérusse, L., & Bouchard, C. (2006) · Obesity · doi:10.1038/oby.2006.71 · Cited by 1,119
Metadata
- 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
- Health Sciences › Nursing › Nutrition and Dietetics › 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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