The DOI matches its Crossref record; 35 of the 35 references it cites were found in a registry or an index.
mRNA Expression Signatures of Human Skeletal Muscle Atrophy Identify a Natural Compound that Increases Muscle Mass
Open accessAbstract
Skeletal muscle atrophy is a common and debilitating condition that lacks a pharmacologic therapy. To develop a potential therapy, we identified 63 mRNAs that were regulated by fasting in both human and mouse muscle, and 29 mRNAs that were regulated by both fasting and spinal cord injury in human muscle. We used these two unbiased mRNA expression signatures of muscle atrophy to query the Connectivity Map, which singled out ursolic acid as a compound whose signature was opposite to those of atrophy-inducing stresses. A natural compound enriched in apples, ursolic acid reduced muscle atrophy and stimulated muscle hypertrophy in mice. It did so by enhancing skeletal muscle insulin/IGF-I signaling and inhibiting atrophy-associated skeletal muscle mRNA expression. Importantly, ursolic acid's effects on muscle were accompanied by reductions in adiposity, fasting blood glucose, and plasma cholesterol and triglycerides. These findings identify a potential therapy for muscle atrophy and perhaps other metabolic diseases.
Overview
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.
Integrity signals
Registry
Cites
Statistics
Verification
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.
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?
In the citing paper
“UA appeared to mediate its effects through enhancement of insulin/IGF-I signaling and a reduction in the expression of the atrophy-associated genes MuRF1 and MAFbx [187]”
From New strategies in sport nutrition to increase exercise performance (2016) · cites this paper as [187]
In the citing paper
“Therefore, it is presently unclear whether UA supplementation in humans can reproduce the anti-atrophy or pro-hypertrophic data reported previously [187].”
From New strategies in sport nutrition to increase exercise performance (2016) · cites this paper as [187]
In the citing paper
“whilst 5 weeks of supplemented diet (0.27% UA) induced hypertrophy [187].”
From New strategies in sport nutrition to increase exercise performance (2016) · cites this paper as [187]
In the citing paper
“UA supplementation in mice (200 mg / kg via i.p. injection twice daily for 7 days) reduced muscle atrophy following denervation”
From New strategies in sport nutrition to increase exercise performance (2016) · cites this paper as [187]
In the citing paper
“Ursolic acid, a pentacyclic triterpenoid abundant in apples, reduces fasting- and denervation-induced muscle atrophy by inhibiting the mRNA expression of MAFbx and MuRF1 and induces skeletal muscle hypertrophy in SD rats [145].”
From Nutraceuticals in the Prevention and Treatment of the Muscle Atrophy (2021) · cites this paper as [145]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Lamb, J., Crawford, E. D., Peck, D., Modell, J. W., Blat, I. C., Wrobel, M. J., Lerner, J., Brunet, J.-P., Subramanian, A., Ross, K. N., et al. (2006) · Science · doi:10.1126/science.1132939 · Cited by 5,257 · cited 3×
“The connectivity score, represented on the y axis, is a measure of the strength of the correlation (Lamb et al., 2006). p < 0.004 for all compounds shown.”
InfluentialIdentification 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 · cited 3×
“Previous studies demonstrated that skeletal muscle atrophy is driven by conserved changes in skeletal muscle gene expression (Bodine et al., 2001a; Sandri et al., 2004).”
Sandri, M., Sandri, C., Gilbert, A., Skurk, C., Calabria, E., Picard, A., Walsh, K., Schiaffino, S., Lecker, S. H., & Goldberg, A. L. (2004) · Cell · doi:10.1016/s0092-8674(04)00400-3 · Cited by 3,012 · cited 2×
“Previous studies demonstrated that skeletal muscle atrophy is driven by conserved changes in skeletal muscle gene expression (Bodine et al., 2001a; Sandri et al., 2004).”
Bodine, 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 · cited 3×
“Previous studies demonstrated that skeletal muscle atrophy is driven by conserved changes in skeletal muscle gene expression (Bodine et al., 2001a; Sandri et al., 2004).”
Stitt, T. N., Drujan, D., Clarke, B. A., Panaro, F., Timofeyva, Y., Kline, W. O., Gonzalez, M., Yancopoulos, G. D., & Glass, D. J. (2004) · Molecular Cell · doi:10.1016/s1097-2765(04)00211-4 · Cited by 1,964 · cited 3×
“We next examined whether ursolic acid might increase Akt activation in C2C12 skeletal myotubes, awell-established in vitro model of skeletal muscle (Sandri et al., 2004; Stitt et al., 2004).”
Pharmacology of oleanolic acid and ursolic acid
Liu, J. (1995) · Journal of Ethnopharmacology · doi:10.1016/0378-8741(95)90032-2 · Cited by 1,431 · cited 1×
“Interestingly, because it exerts beneficial effects in animal models of diabetes and hyperlipidemia (Liu, 1995; Wang et al., 2009), ursolic acid is thought to be the active component in a variety of folkloric antidiabetic herbal medicines (Liu, 1995, 2005).”
Normal growth and development in the absence of hepatic insulin-like growth factor I
Yakar, S., Liu, J., STANNARD, B. S., Butler, A. A., Accili, D., Sauer, B., & LeRoith, D. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.13.7324 · Cited by 1,418 · cited 1×
“We also measured the effect of ursolic acid on plasma IGF-I levels, which primarily reflect growth hormone-mediated hepatic IGF-I production (Yakar et al., 1999).”
Klaman, L. D., Boss, O., Peroni, O. D., Kim, J. K., Martino, J. L., Zabolotny, J. M., Moghal, N., Lubkin, M., Kim, Y.-B., Sharpe, A. H., et al. (2000) · Molecular and Cellular Biology · doi:10.1128/mcb.20.15.5479-5489.2000 · Cited by 1,235 · cited 1×
“However, neither global nor muscle-specific PTP1B knockout mice were found to possess increased muscle mass (Delibegovic et al., 2007; Klaman et al., 2000).”
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 2×
“, 2005) and stimulatesmuscle hypertrophy (Barton-Davis et al., 1998; Musaro et al., 2001).”
Sandri, M., Lin, J., Handschin, C., Yang, W., Arany, Z. P., Lecker, S. H., Goldberg, A. L., & Spiegelman, B. M. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0607795103 · Cited by 974 · cited 1×
“Of these, PGC-1a mRNA encodes a protein that inhibits atrophy-associated gene expression and skeletal muscle atrophy in mice (Sandri et al., 2006).”
Cited by
Sorted by citations
Drug repurposing: progress, challenges and recommendations
Pushpakom, S., Iorio, F., Eyers, P. A., Escott, K. J., Hopper, S., Wells, A., Doig, A., Guilliams, T., Latimer, J., McNamee, C., et al. (2019) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2018.168 · Cited by 4,718
Rapa, S. F., Iorio, B. R. D., Campiglia, P., Heidland, A., & Marzocco, S. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms21010263 · Cited by 577
Sarcopenia in chronic kidney disease: what have we learned so far?
Sabatino, A., Cuppari, L., Stenvinkel, P., Lindholm, B., & Avesani, C. M. (2020) · Journal of Nephrology · doi:10.1007/s40620-020-00840-y · Cited by 549
Kibble, M., Saarinen, N., Tang, J. P., Wennerberg, K., Mäkelä, S., & Aittokallio, T. A. (2015) · Natural Product Reports · doi:10.1039/c5np00005j · Cited by 508
Skeletal muscle atrophy: From mechanisms to treatments
Yin, L., Li, N., Jia, W., Wang, N., Liang, M., Yang, X., & Du, G. (2021) · Pharmacological Research · doi:10.1016/j.phrs.2021.105807 · Cited by 423
Metadata
- Authors
- Kunkel, S. D., Suneja, M., Ebert, S. M., Bongers, K. S., Fox, D. K., Malmberg, S. E., Alipour, F., Shields, R. K., & Adams, C. M.
- Affiliations
- University of Iowa (US)
- Corresponding author
- Adams, Christopher M.
- ORCID
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2011-06
- Volume
- 13
- Issue
- 6
- Pages
- 627-638
- ISSN
- 1550-4131 (ISSN-L)
- PMC
- PMC3120768
- OpenAlex
- W2099582158
- Cited by
- 345
- References
- 35
- Citations by year
- 2026: 15 · 2025: 17 · 2024: 18 · 2023: 22 · 2022: 23 · 2021: 36 · 2020: 24 · 2019: 35 · 2018: 26 · 2017: 24 · 2016: 25 · 2015: 27 · 2014: 16 · 2013: 19 · 2012: 16
- FWCI
- 6.71
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 777 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- American Diabetes Association (1R01AR059115-01)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases
- U.S. Department of Veterans Affairs
- Doris Duke Charitable Foundation
- Institute of Clinical and Translational Sciences
- National Institutes of Health (HL007121, T32 GM073610)
- University of Georgia Research Foundation
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Health Sciences › Medicine › Physiology (medical) › Nutrition and Health in Aging
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- Keywords
- skeletal muscle atrophy, ursolic acid, muscle hypertrophy, fasting, spinal cord injury, mRNA expression signature, adiposity, metabolic disorders, natural compounds, apple
- MeSH terms
- Ursolic Acid, Animals, Cell Line, Fasting, Gene Expression Regulation, Hindlimb, Humans, Insulin, Insulin-Like Growth Factor I, Mice, Inbred C57BL, Muscle Denervation, Muscular Atrophy, Triterpenes, Signal Transduction, Gene Expression, Muscle, Skeletal, Muscle Fibers, Skeletal, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling, Mice, Muscle Strength
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
