Systems-Based Discovery of Tomatidine as a Natural Small Molecule Inhibitor of Skeletal Muscle Atrophy
Open accessAbstract
Skeletal muscle atrophy is a common and debilitating condition that lacks an effective therapy. To address this problem, we used a systems-based discovery strategy to search for a small molecule whose mRNA expression signature negatively correlates to mRNA expression signatures of human skeletal muscle atrophy. This strategy identified a natural small molecule from tomato plants, tomatidine. Using cultured skeletal myotubes from both humans and mice, we found that tomatidine stimulated mTORC1 signaling and anabolism, leading to accumulation of protein and mitochondria, and ultimately, cell growth. Furthermore, in mice, tomatidine increased skeletal muscle mTORC1 signaling, reduced skeletal muscle atrophy, enhanced recovery from skeletal muscle atrophy, stimulated skeletal muscle hypertrophy, and increased strength and exercise capacity. Collectively, these results identify tomatidine as a novel small molecule inhibitor of muscle atrophy. Tomatidine may have utility as a therapeutic agent or lead compound for skeletal muscle atrophy.
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Tomatidine stimulates mTORC1 signaling resulting in the accumulation of protein and mitochondria, and ultimately cell growth in C2C12 myoblasts and human skeletal myotubes.
“Tomatidine also stimulates mTORC1 signaling resulting in the accumulation of protein and mitochondria, and ultimately, cell growth in C2C12 myoblasts and human skeletal myotubes.”
From Nutraceuticals in the Prevention and Treatment of the Muscle Atrophy (2021) · cites this paper as [136]
Tomatidine inhibits age-related skeletal muscle atrophy via activating skeletal muscle mTORC1 signaling in C57BL/6 mice.
“Tomatidine, a natural small molecule alkaloid abundant in unripe tomatoes, inhibits age-related skeletal muscle atrophy via activating skeletal muscle mTORC1 signaling in C57BL/6 mice.”
From Nutraceuticals in the Prevention and Treatment of the Muscle Atrophy (2021) · cites this paper as [136]
Tomatidine stimulates skeletal muscle hypertrophy and increases strength and exercise capacity.
“Moreover, tomatidine stimulates skeletal muscle hypertrophy and increases strength and exercise capacity [136].”
From Nutraceuticals in the Prevention and Treatment of the Muscle Atrophy (2021) · cites this paper as [136]
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- Authors
- Dyle, M. C., Ebert, S. M., Cook, D. P., Kunkel, S. D., Fox, D. K., Bongers, K. S., Bullard, S. A., Dierdorff, J. M., & Adams, C. M.
- Affiliations
- University of Iowa (US)
- Corresponding author
- Adams, Christopher M.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2014-05
- Volume
- 289
- Issue
- 21
- Pages
- 14913-14924
- ISSN
- 0021-9258 (ISSN-L)
- PMC
- PMC4031541
- OpenAlex
- W2046746548
- Cited by
- 138
- References
- 85
- Citations by year
- 2026: 9 · 2025: 4 · 2024: 8 · 2023: 16 · 2022: 10 · 2021: 19 · 2020: 13 · 2019: 15 · 2018: 10 · 2017: 14 · 2016: 9 · 2015: 6 · 2014: 4
- FWCI
- 4.51
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (AR059115-04, 1F31AG04603801, HL07638-27, F30AG04496401, F30AG04330401)
- 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
- Health Sciences › Medicine › Physiology › Nutrition and Health in Aging
- Keywords
- tomatidine, skeletal muscle atrophy, mTORC1 signaling, muscle hypertrophy, tomato, mRNA expression signature, skeletal muscle myotubes, muscle strength, exercise capacity, mitochondrial accumulation
- MeSH terms
- Mechanistic Target of Rapamycin Complex 1, Animals, Cell Line, Cells, Cultured, Humans, Male, Mice, Inbred C57BL, Mitochondria, Muscle, Muscle Proteins, Muscular Atrophy, Tomatine, Immunoblotting, Signal Transduction, Gene Expression, Muscle, Skeletal, Muscle Fibers, Skeletal, HL-60 Cells, Reverse Transcriptase Polymerase Chain Reaction, Myoblasts, Skeletal, Cell Line, Tumor, Multiprotein Complexes, Mice, Drug Discovery, TOR Serine-Threonine Kinases, MCF-7 Cells
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