Cited by 138Muscle Physiology and DisordersMuscle metabolism and nutritionNutrition and Health in Aging

Systems-Based Discovery of Tomatidine as a Natural Small Molecule Inhibitor of Skeletal Muscle Atrophy

Open access
Dyle, Michael C., Ebert, Scott M., Cook, Daniel P., Kunkel, Steven D., Fox, Daniel K., Bongers, Kale S., Bullard, Steven A., Dierdorff, Jason M. +1 more·2014·Journal of Biological Chemistry

Abstract

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.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1074/jbc.m114.556241

Cites

85 of 85 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • 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.”
  • 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.”
  • Tomatidine stimulates skeletal muscle hypertrophy and increases strength and exercise capacity.

    “Moreover, tomatidine stimulates skeletal muscle hypertrophy and increases strength and exercise capacity [136].”

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

1 retracted

Flagged first, then by citations

Cited by

Sorted by citations

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)
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
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

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.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review