The DOI matches its Crossref record; 54 of the 54 references it cites were found in a registry or an index.
Growth and differentiation factor 15 is secreted by skeletal muscle during exercise and promotes lipolysis in humans
Open accessAbstract
We hypothesized that skeletal muscle contraction produces a cellular stress signal, triggering adipose tissue lipolysis to sustain fuel availability during exercise. The present study aimed at identifying exercise-regulated myokines, also known as exerkines, able to promote lipolysis. Human primary myotubes from lean healthy volunteers were submitted to electrical pulse stimulation (EPS) to mimic either acute intense or chronic moderate exercise. Conditioned media (CM) experiments with human adipocytes were performed. CM and human plasma samples were analyzed using unbiased proteomic screening and/or ELISA. Real-time qPCR was performed in cultured myotubes and muscle biopsy samples. CM from both acute intense and chronic moderate exercise increased basal lipolysis in human adipocytes. Growth and differentiation factor 15 (GDF15) gene expression and secretion increased rapidly upon skeletal muscle contraction. GDF15 protein was upregulated in CM from both acute and chronic exercise–stimulated myotubes. We further showed that physiological concentrations of recombinant GDF15 protein increased lipolysis in human adipose tissue, while blocking GDF15 with a neutralizing antibody abrogated EPS CM-mediated lipolysis. We herein provide the first evidence to our knowledge that GDF15 is a potentially novel exerkine produced by skeletal muscle contraction and able to target human adipose tissue to promote lipolysis.
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“acute exercise in humans also releases additional molecules79, such as growth and differentiation factor 15 (GDF15)80 and IL-6 (REF.81), which also affect lipolysis”
From Exerkines in health, resilience and disease (2022) · cites this paper as [80]
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Cites
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Exercise as medicine - evidence for prescribing exercise as therapy in 26 different chronic diseases
Pedersen, B. K., & Saltin, B. (2015) · Scandinavian Journal of Medicine & Science in Sports · doi:10.1111/sms.12581 · Cited by 3,514
Muscles, exercise and obesity: skeletal muscle as a secretory organ
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Integrative Biology of Exercise
Hawley, J. A., Hargreaves, M., Joyner, M. J., & Zierath, J. R. (2014) · Cell · doi:10.1016/j.cell.2014.10.029 · Cited by 1,152
GFRAL is the receptor for GDF15 and the ligand promotes weight loss in mice and nonhuman primates
Mullican, S. E., Lin-Schmidt, X., Chin, C.-N., Chavez, J. A., Furman, J. L., Armstrong, A. A., Beck, S. C., South, V. J., Dinh, T. Q., Cash-Mason, T. D., et al. (2017) · Nature Medicine · doi:10.1038/nm.4392 · Cited by 774
Interleukin-6 stimulates lipolysis and fat oxidation in humans
van Hall, G., Steensberg, A., Sacchetti, M., Fischer, C., Keller, C., Schjerling, P., Hiscock, N., Møller, K., Saltin, B., Febbraio, M. A., et al. (2003) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2002-021687 · Cited by 767
Perseghin, G., Price, T. B., Petersen, K. F., Roden, M., Cline, G. W., Gerow, K., Rothman, D. L., & Shulman, G. I. (1996) · New England Journal of Medicine · doi:10.1056/nejm199610313351804 · Cited by 699
The metabolic effects of GDF15 are mediated by the orphan receptor GFRAL
Emmerson, P. J., Wang, F., Du, Y., Liu, Q., Pickard, R. T., Gonciarz, M. D., Coskun, T., Hamang, M. J., Sindelar, D. K., Ballman, K. K., et al. (2017) · Nature Medicine · doi:10.1038/nm.4393 · Cited by 675
GFRAL is the receptor for GDF15 and is required for the anti-obesity effects of the ligand
Yang, L., Chang, C.-C., Sun, Z., Madsen, D., Zhu, H., Padkjær, S. B., Wu, X., Huang, T., Hultman, K., Paulsen, S. J., et al. (2017) · Nature Medicine · doi:10.1038/nm.4394 · Cited by 668
Non-Homeostatic Body Weight Regulation Through a Brainstem-Restricted Receptor for GDF15
Hsu, J.-Y., Crawley, S., Chen, M., Ayupova, D. A., Lindhout, D. A., Higbee, J., Kutach, A., Joo, W., Gao, Z., Fu, D., et al. (2017) · Nature · doi:10.1038/nature24042 · Cited by 616
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Exerkines in health, resilience and disease
Chow, L. S., Gerszten, R. E., Taylor, J. M., Pedersen, B. K., van Praag, H., Trappe, S., Febbraio, M. A., Galis, Z. S., Gao, Y., Haus, J. M., et al. (2022) · Nature Reviews Endocrinology · doi:10.1038/s41574-022-00641-2 · Cited by 927
Self-citationGDF15: emerging biology and therapeutic applications for obesity and cardiometabolic disease
Wang, D., Day, E. A., Townsend, L. K., Djordjevic, D., Jørgensen, S. B., & Steinberg, G. R. (2021) · Nature Reviews Endocrinology · doi:10.1038/s41574-021-00529-7 · Cited by 543
Exercise and metabolic health: beyond skeletal muscle
Thyfault, J. P., & Bergouignan, A. (2020) · Diabetologia · doi:10.1007/s00125-020-05177-6 · Cited by 455
“A novel exerkine produced by skeletal muscle contraction has recently been identified that targets human adipose tissue to promote lipolysis, namely, growth and differentiation factor 15 (GDF15) [71].”
BackgroundInfluentialInflammation and Skeletal Muscle Wasting During Cachexia
Webster, J. M., Kempen, L. J. A. P., Hardy, R. S., & Langen, R. C. J. (2020) · Frontiers in Physiology · doi:10.3389/fphys.2020.597675 · Cited by 372
Cachexia: A systemic consequence of progressive, unresolved disease
Ferrer, M., Anthony, T. G., Ayres, J. S., Biffi, G., Brown, J. C., Caan, B. J., Feliciano, E. M. C., Coll, A. P., Dunne, R. F., Goncalves, M. D., et al. (2023) · Cell · doi:10.1016/j.cell.2023.03.028 · Cited by 282
Metadata
- Authors
- Laurens, C., Parmar, A., Murphy, E., Carper, D., Lair, B., Maes, P., Vion, J., Boulet, N., Fontaine, C., Marquès, M., Larrouy, D., Harant, I., Thalamas, C., Montastier, E., Caspar-Bauguil, S., Bourlier, V., Tavernier, G., Grolleau, J.-L., Bouloumié, A., Langin, D., Viguerie, N., Bertile, F., Blanc, S., de Glisezinski, I., O’Gorman, D., & Moro, C.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Université Toulouse III - Paul Sabatier (FR)
- Dublin City University (IE)
- Inserm, UMR1048, Institute of Metabolic and Cardiovascular Diseases, Toulouse, France.
- Inserm (FR)
- Centre d’Investigation Clinique 1436 (FR)
- ORCID
- Laurens, Claire
- Murphy, Enda
- Carper, Deborah
- Lair, Benjamin
- Vion, Julie
- Boulet, Nathalie
- Fontaine, Coralie
- Larrouy, Dominique
- Harant, Isabelle
- Thalamas, Claire
- Montastier, Emilie
- Caspar-Bauguil, Sylvie
- Bourlier, Virginie
- Tavernier, Geneviève
- Bouloumié, Anne
- Langin, Dominique
- Viguerie, Nathalie
- Bertile, Fabrice
- de Glisezinski, Isabelle
- O’Gorman, Donal
- Moro, Cedric
- Venue
- JCI Insight
- Published
- 2020-03-26
- Volume
- 5
- Issue
- 6
- Pages
- e131870
- ISSN
- 2379-3708 (ISSN-L)
- PMC
- PMC7213799
- OpenAlex
- W3008261843
- Cited by
- 135
- References
- 54
- Citations by year
- 2026: 16 · 2025: 24 · 2024: 25 · 2023: 13 · 2022: 20 · 2021: 27 · 2020: 10
- FWCI
- 13.17
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- JCI Insight (publishedVersion, cc-by)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion, other-oa)
- Funders
- Agence Nationale de la Recherche (ANR-10-INBS-0008, ANR-10-INSB-08, ANR-10-INSB-08–03, ANR-10)
- Institut National de la Santé et de la Recherche Médicale
- Centre National d’Etudes Spatiales
- Centre National de la Recherche Scientifique
- Institut Universitaire de France
- Société Française de Nutrition
- Région Occitanie Pyrénées-Méditerranée
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › GDF15 and Related Biomarkers
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- Health Sciences › Medicine › Physiology (medical) › Exercise and Physiological Responses
- Keywords
- growth and differentiation factor 15, GDF15, myokines, exerkines, skeletal muscle contraction, physical activity, lipolysis, adipose tissue, myotubes, electrical pulse stimulation
- MeSH terms
- Adult, Humans, Lipolysis, Male, Exercise, Muscle, Skeletal, Growth Differentiation Factor 15
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