From gains to liver pain: when exercise training goes too far
Open accessAbstract
A recent study from Liu et al. described the role of skeletal muscle-derived extracellular vesicles in promoting liver fibrosis as an outcome of chronic overtraining in mice. Here, we highlight this work and discuss its implications within the fields of exercise physiology and inter-organ communication.
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
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?
Overtraining caused excessive lactate accumulation in skeletal muscle and the subsequent formation of lactate bodies, thereby inducing hepatocyte apoptosis and liver fibrosis via the MCL1-BAX/BAK axis.
“Recent evidence demonstrated that overtraining caused excessive lactate accumulation in skeletal muscle and the subsequent formation of lactate bodies, thereby inducing hepatocyte apoptosis and liver fibrosis via the MCL1-BAX/BAK axis [401, 402].”
From Mechanisms, efficacy, and future perspectives of cellular-based therapies for liver fibrosis/cirrhosis: focusing on mesenchymal stromal cells (2025) · cites this paper as [402]
The Research summary (page unavailable) reports overtraining-associated lactate accumulation in skeletal muscle, extracellular-vesicle-mediated hepatocyte apoptosis, liver fibrosis, and MCL1 downregulation. It does not describe the formation of “lactate bodies” or identify a BAX/BAK axis; the mechanistic evidence it summarizes comes principally from mice and cultured cells. (LLM, conf=0.87)
Experimental — accuracy not yet measured
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
Extracellular Vesicles Provide a Means for Tissue Crosstalk during Exercise
Whitham, M., Parker, B. L., Friedrichsen, M. H., Hingst, J. R., Hjorth, M., Hughes, W. E., Egan, C. L., Cron, L., Watt, K. I., Kuchel, R. P., et al. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2017.12.001 · Cited by 689 · see citing works
A brief history of nearly EV‐erything – The rise and rise of extracellular vesicles
Couch, Y., Buzás, E. I., Vizio, D. D., Gho, Y. S., Harrison, P., Hill, A. F., Lötvall, J. O., Raposo, G., Stahl, P. D., Théry, C., et al. (2021) · Journal of Extracellular Vesicles · doi:10.1002/jev2.12144 · Cited by 564 · see citing works
Flockhart, M., Nilsson, L. C., Tais, S., Ekblom, B. T., Apró, W., & Larsen, F. J. (2021) · Cell Metabolism · doi:10.1016/j.cmet.2021.02.017 · Cited by 264 · see citing works
Brahmer, A., Neuberger, E. W. I., Esch-Heisser, L., Haller, N., Jørgensen, M. M., Bæk, R., Möbius, W., Simon, P. D., & Krämer‐Albers, E. (2019) · Journal of Extracellular Vesicles · doi:10.1080/20013078.2019.1615820 · Cited by 245 · see citing works
Muscle releases alpha-sarcoglycan positive extracellular vesicles carrying miRNAs in the bloodstream
Guescini, M., Canonico, B., Lucertini, F., Maggio, S., Annibalini, G., Barbieri, E., Luchetti, F., Papa, S., & Stocchi, V. (2015) · PLoS ONE · doi:10.1371/journal.pone.0125094 · Cited by 228 · see citing works
Bei, Y., Xu, T., Lv, D., Yu, P., Xu, J., Che, L., Das, A., Tigges, J., Toxavidis, V., Ghiran, I. C., et al. (2017) · Basic Research in Cardiology · doi:10.1007/s00395-017-0628-z · Cited by 201 · see citing works
Castaño, C., Mirasierra, M., Vallejo, M., Novials, A., & Párrizas, M. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2016112117 · Cited by 154 · see citing works
Ma, S., Xing, X., Huang, H., Gao, X., Xu, X., Yang, J., Liao, C., Zhang, X., Liu, J., Tian, W., et al. (2023) · Cell Metabolism · doi:10.1016/j.cmet.2023.10.013 · Cited by 145 · see citing works
The role of extracellular vesicles in skeletal muscle and systematic adaptation to exercise
Vechetti, I. J., Valentino, T., Mobley, C. B., & McCarthy, J. J. (2021) · The Journal of Physiology · doi:10.1113/jp278929 · Cited by 141 · see citing works
Self-citationMechanical overload‐induced muscle‐derived extracellular vesicles promote adipose tissue lipolysis
Vechetti, I. J., Peck, B. D., Wen, Y., Walton, R. G., Valentino, T. R., Alimov, A. P., Dungan, C. M., Pelt, D. W. V., von Walden, F., Alkner, B. A., et al. (2021) · The FASEB Journal · doi:10.1096/fj.202100242r · Cited by 105 · see citing works
Self-citationde Oliveira, G. P., Porto, W. F., Palu, C. C., Pereira, L. M., Petriz, B. A., de Almeida, J. A., Viana, J., Filho, N. N. A., Franco, O. L., & Pereira, R. W. (2018) · Frontiers in Physiology · doi:10.3389/fphys.2018.00532 · Cited by 104 · see citing works
Muscle-derived small extracellular vesicles induce liver fibrosis during overtraining
Liu, Y., Zhou, R., Guo, Y., Hu, B., Xie, L., An, Y., Wen, J., Liu, Z., Zhou, M., Kuang, W., et al. (2025) · Cell Metabolism · doi:10.1016/j.cmet.2024.12.005 · Cited by 78 · see citing works
Wang, Y., Liu, Y., Zhang, S., Li, N., Xing, C., Wang, C., Wang, J., Wei, M., Yang, G., & Yuan, L. (2023) · Aging and Disease · doi:10.14336/ad.2022.1131 · Cited by 44 · see citing works
Physiology and Pathophysiology of Marathon Running: A narrative Review
Braschler, L., Nikolaidis, P. Τ., Thuany, M., Chlíbková, D., Rosemann, T. J., Weiss, K., Wilhelm, M., & Knechtle, B. (2025) · Sports Medicine - Open · doi:10.1186/s40798-025-00810-3 · Cited by 36 · see citing works
Burke, B. I., Ismaeel, A., Long, D. E., Depa, L. A., Coburn, P. T., Goh, J. Z., Saliu, T. P., Walton, B. J., Vechetti, I. J., Peck, B. D., et al. (2024) · JCI Insight · doi:10.1172/jci.insight.182589 · Cited by 31 · see citing works
Self-citationMcIlvenna, L. C., Parker, H., Seabright, A. P., Sale, B., Anghileri, G., Weaver, S. R., Lucas, S. J. E., & Whitham, M. (2023) · The Journal of Physiology · doi:10.1113/jp284047 · Cited by 27 · see citing works
Mieszkowski, J., Stankiewicz, B., Kochanowicz, A., Niespodziński, B., Borkowska, A., Sikorska, K., Daniłowicz‐Szymanowicz, L., Brzezinska, P. B., & Antosiewicz, J. (2021) · Frontiers in Physiology · doi:10.3389/fphys.2021.731889 · Cited by 23 · see citing works
Conkright, W. R., Kargl, C. K., Hubal, M. J., Tiede, D., Beckner, M. E., Sterczala, A. J., Krajewski, K. T., Martin, B. J., Flanagan, S. D., Greeves, J. P., et al. (2024) · Medicine & Science in Sports & Exercise · doi:10.1249/mss.0000000000003408 · Cited by 16 · see citing works
Skeletal muscle hypertrophy: cell growth is cell growth
Burke, B. I., Ismaeel, A., von Walden, F., Murach, K. A., & McCarthy, J. J. (2024) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00418.2024 · Cited by 15 · see citing works
Self-citationBurke, B. I., Ismaeel, A., & McCarthy, J. J. (2024) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00362.2024 · Cited by 15 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Pan, X., Gao, T., & Wang, B. (2025) · Cell & Bioscience · doi:10.1186/s13578-025-01520-9 · Cited by 2 · see citing works
“Recent evidence demonstrated that over-training caused excessive lactate accumulation in skeletal muscle and the subsequent formation of lactate bodies, thereby inducing hepatocyte apoptosis and liver fibrosis via the MCL1-BAX/BAK axis [401, 402].”
- Authors
- Burke, B. I., McCarthy, J. J., & Ismaeel, A.
- Affiliations
- University of Kentucky (US)
- Corresponding author
- Ismaeel, Ahmed
- Venue
- Extracellular Vesicles and Circulating Nucleic Acids
- Publisher
- OAE Publishing Inc.
- Published
- 2025-06-25
- Volume
- 6
- Issue
- 2
- Pages
- 324-7
- ISSN
- 2767-6641 (ISSN-L)
- PMC
- PMC12367453
- OpenAlex
- W4411592702
- Cited by
- 1
- References
- 20
- Citations by year
- 2025: 1
- FWCI
- 0.34
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by
- Locations
- Extracellular Vesicles and Circulating Nucleic Acids (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- UKnowledge (University of Kentucky) (submittedVersion)
- Topics
- Health Sciences › Medicine › Rehabilitation › Exercise and Physiological Responses
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Keywords
- liver fibrosis, inter-organ communication, exercise physiology, liver pain
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
