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 releases molecules such as GDF15 and IL-6 that affect lipolysis, in addition to adrenaline.
“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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GDF15 in Appetite and Exercise: Essential Player or Coincidental Bystander?
Klein, A. B., Kleinert, M., Richter, E. A., & Clemmensen, C. (2021) · Endocrinology · doi:10.1210/endocr/bqab242 · Cited by 49 · see citing works
Cytokines and exosomal miRNAs in skeletal muscle–adipose crosstalk
Guo, L., Quan, M., Pang, W., Yin, Y., & Li, F. (2023) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2023.07.006 · Cited by 48 · see citing works
GDF15 Mediates the Effect of Skeletal Muscle Contraction on Glucose-Stimulated Insulin Secretion
Zhang, H., Mulya, A., Nieuwoudt, S., Vandanmagsar, B., McDowell, R. E., Heintz, E. C., Zunica, E. R. M., Collier, J. J., Bozadjieva-Kramer, N., Seeley, R. J., et al. (2023) · Diabetes · doi:10.2337/db22-0019 · Cited by 45 · see citing works
“These data are consistent with those in recent reports showing increasing GDF15 secretion after both acute and chronic exposure to EPS (56).”
ResultInfluence of Acute and Chronic Exercise on Abdominal Fat Lipolysis: An Update
Laurens, C., de Glisezinski, I., Larrouy, D., Harant, I., & Moro, C. (2020) · Frontiers in Physiology · doi:10.3389/fphys.2020.575363 · Cited by 42 · see citing works
Self-citationPoffé, C., Robberechts, R., Podlogar, T., Kusters, M., Debevec, T., & Hespel, P. (2021) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00198.2021 · Cited by 45 · see citing works
Growth and differentiation factor-15: A link between inflammaging and cardiovascular disease
Nyárády, B. B., Kiss, L. Z., Bagyura, Z., Merkely, B. P., Dósa, E., Láng, O., Kőhidai, L., & Pállinger, É. (2024) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2024.116475 · Cited by 44 · see citing works
Macrophages as a Source and Target of GDF-15
Silva-Bermúdez, L. S., Klüter, H., & Kzhyshkowska, J. G. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25137313 · Cited by 44 · see citing works
“Circulating GDF-15 increases with age and is unaffected by gender [35,42,94].”
BackgroundAl‐Mudares, F., Reddick, S. J., Ren, J. L., Venkatesh, A., Zhao, C., & Lingappan, K. (2020) · Frontiers in Medicine · doi:10.3389/fmed.2020.594137 · Cited by 44 · see citing works
“Low body mass index (BMI) is a risk factor for exaggerated decline in the lung function, and is an independent predictor of the overall mortality in COPD (64), and is a bad prognostic indicator in the BODE index; which is used to predict the mortality risk among COPD patients (65).”
BackgroundGDF15 is an exercise-induced hepatokine regulated by glucagon and insulin in humans
Plomgaard, P., Hansen, J. S., Townsend, L. K., Gudiksen, A., Secher, N. H., Clemmesen, J. O., Støving, R. K., Goetze, J. P., Wright, D. C., & Pilegaard, H. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.1037948 · Cited by 39 · see citing works
“Cultured muscle cells exposed to electrical pulse stimulation secrete GDF15 to the medium (30), and despite a low expression in the skeletal muscles, exercise induces a transient increase in muscle GDF15 mRNA in mice (31).”
BackgroundGFRAL Is Widely Distributed in the Brain and Peripheral Tissues of Mice
Fichtner, K., Kalwa, H., Lin, M., Gong, Y., Müglitz, A., Kluge, M., & Krügel, U. (2024) · Nutrients · doi:10.3390/nu16050734 · Cited by 37 · see citing works
“…or endocrine properties of GDF15 have been discussed repeatedly, particularly regarding the adjustment of metabolic activity, and may be in line with the reported enhancement of GDF15 expression in the liver, heart and muscles after physical exercise, as reviewed by Wang (2021) [4,8,20,42,43].”
BackgroundThe PPARβ/δ-AMPK Connection in the Treatment of Insulin Resistance
Aguilar-Recarte, D., Palomer, X., Wahli, W., & Vázquez‐Carrera, M. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22168555 · Cited by 37 · see citing works
“Although additional studies are needed to reject the potential involvement of GFRAL on the GDF15-mediated antidiabetic effects of PPARβ/δ agonists, as Gfral mRNA is absent in C2C12 cells [49,55] and skeletal muscle [49,59], the GDF15-mediated activation of AMPK in isolated skeletal muscle and cultured myotubes seems t…”
BackgroundNew Horizon: Exercise and a Focus on Tissue-Brain Crosstalk
Townsend, L. K., MacPherson, R. E. K., & Wright, D. C. (2021) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgab333 · Cited by 35 · see citing works
Emerging Roles of GDF15 in Metabolic and Cardiovascular Diseases
Tian, T., Liu, M., Little, P. J., Strijdom, H., Weng, J., & Xu, S. (2025) · Research · doi:10.34133/research.0832 · Cited by 30 · see citing works
“This effect is mediated through both SMAD and non-SMAD signaling pathways, which are involved in the regulation of lipid metabolism [ 104 ].”
Altered GDF15 and FGF21 Levels in Response to Strenuous Exercise: A Study in Marathon Runners
Campderrós, L., Sánchez‐Infantes, D., Villarroya, J., Nescolarde, L., Bayés‐Genís, A., Cereijo, R., Roca, E., & Villarroya, F. (2020) · Frontiers in Physiology · doi:10.3389/fphys.2020.550102 · Cited by 30 · see citing works
“For GDF15, a recent study indicated that the rise in GDF15 after a single bout of exercise is associated with increased GDF15 gene expression in skeletal muscle (Laurens et al., 2020).”
BackgroundImbert, A., Vialaneix, N., Marquis, J., Vion, J., Charpagne, A., Métairon, S., Laurens, C., Moro, C., Boulet, N., Walter, O., et al. (2021) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgab621 · Cited by 28 · see citing works
“The negative association between 294 change in plasma GDF15 and change in BMI during the LCD was previously reported (32), but no 295”
BackgroundSelf-citationExercise-regulated lipolysis: Its role and mechanism in health and diseases
Zhu, J., & Guo, L. (2024) · Journal of Advanced Research · doi:10.1016/j.jare.2024.11.031 · Cited by 31 · see citing works
“After conditioned media culture, it was found that the culture media of exercise-stimulated myotubes led to higher levels of FFAs and glycerol released from human adipocytes while blocking GDF15 with a neutralizing antibody blunted this effect [38].”
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
“Examples of myokines that have been shown to influence adipocyte function include IL-6 and growth and differentiation factor 15 (GDF15) (46, 47).”
Discovery of thymosin β4 as a human exerkine and growth factor
González-Franquesa, A., Stocks, B., Borg, M. L., Kuefner, M., Dalbram, E., Nielsen, T. S., Agrawal, A., Pankratova, S., Chibalin, A., Karlsson, H., et al. (2021) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00263.2021 · Cited by 28 · see citing works
GDF15, an Emerging Player in Renal Physiology and Pathophysiology
Lasaad, S., & Crambert, G. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25115956 · Cited by 27 · see citing works
“It has also been demonstrated that GDF15 increases in response to physical exertion, where it is produced by muscles [27].”
BackgroundExercise, Mitohormesis, and Mitochondrial ORF of the 12S rRNA Type-C (MOTS-c)
Yoon, T. K., Lee, C. H., Kwon, O., & Kim, M. (2022) · Diabetes & Metabolism Journal · doi:10.4093/dmj.2022.0092 · Cited by 27 · see citing works
Breen, D. M., Jagarlapudi, S., Patel, A. R., Zou, C. H., Joaquim, S., Li, X., Kang, L., Pang, J., Hales, K. J., Ziso-Qejvanaj, E., et al. (2021) · iScience · doi:10.1016/j.isci.2021.102554 · Cited by 26 · see citing works
Aging Aggravates Cachexia in Tumor-Bearing Mice
Geppert, J., Walth-Hummel, A. A., Terrón-Expósito, R., Kaltenecker, D., Morigny, P., Machado, J., Becker, M., Simoes, E., Lima, J. D. C. C., Daniel, C., et al. (2021) · Cancers · doi:10.3390/cancers14010090 · Cited by 26 · see citing works
“Gdf15 was shown to be expressed in skeletal muscle under different stress conditions [40,41].”
BackgroundBuchholz, K., Antosik, P., Grzanka, D., Gagat, M., Smolińska, M., Grzanka, A., Gzil, A., Kasperska, A., & Klimaszewska‐Wiśniewska, A. (2021) · Journal of Cancer · doi:10.7150/jca.55511 · Cited by 25 · see citing works
“The highest expression of GFRAL has been detected in neurons of brainstem area postrema and nucleus of the solitary tract in mice and humans [27], but its presence has also been confirmed in human adipose tissue [29].”
BackgroundPaepe, B. D. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232113180 · Cited by 23 · see citing works
“The skeletal muscle tissue is a possible source, stimulated to produce GDF-15 by muscle contraction [120].”
BackgroundChang, J. S., & Namkung, J. (2021) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph18052242 · Cited by 22 · see citing works
“However, other studies addressing the promotion of weight loss in obese adults and/or elderly individuals have reported that a lifestyle-modifying intervention combining exercise and diet restriction increased the levels of circulating GDF15 [59,60].”
BackgroundNutritional Mechanisms of Cancer Cachexia
Compton, S. L. E., Heymsfield, S. B., & Brown, J. C. (2024) · Annual Review of Nutrition · doi:10.1146/annurev-nutr-062122-015646 · Cited by 21 · see citing works
Cancer- and cardiac-induced cachexia: same fate through different inflammatory mediators?
Nogueira‐Ferreira, R., Sousa‐Nunes, F., Leite-Moreira, A. F., Moreira‐Costa, L., Vitorino, R. M. P., Santos, L. L., Moreira‐Gonçalves, D., & Ferreira, R. M. (2022) · Inflammation Research · doi:10.1007/s00011-022-01586-y · Cited by 21 · see citing works
“However, it is unclear if these effects are mediated by the GFRAL receptor [99].”
BackgroundTargeting the GDF15 Signalling for Obesity Treatment: Recent Advances and Emerging Challenges
Zhang, J., Sun, J., Li, J., & Xia, H. (2024) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.70251 · Cited by 20 · see citing works
Metabolic Messenger: growth differentiation factor 15
Breit, S. N., & Tsai, V. W.-W. (2025) · Nature Metabolism · doi:10.1038/s42255-025-01353-3 · Cited by 20 · see citing works
“Furthermore, elevated GDF15 has been linked to the activation of the hypothalamic–pituitary–adrenal axis, resulting in increased corticosterone levels and enhanced fatty acid oxidation in the liver, which is consistent with GDF15’s role in promoting lipolysis 123,124 .”
Beneficial Effects of Low-Grade Mitochondrial Stress on Metabolic Diseases and Aging
Min, S. H., Kang, G. M., Park, J.-W., & Kim, M. (2024) · Yonsei Medical Journal · doi:10.3349/ymj.2023.0131 · Cited by 19 · see citing works
“Exercise-induced mitochondrial stress increases skeletal muscle expression levels of both factors, 74,176 and these mitokines are released into the systemic circulation to stimulate adipose tissue thermogenesis, lipolysis, and fatty acid oxidation, leading to the alleviation of obesity and…”
BackgroundDistinct roles of UVRAG and EGFR signaling in skeletal muscle homeostasis
Kim, M. J., Febbraro, D., Farkona, S., Gillmore, T., Son, J. E., Regeenes, R., Chang, H. H., Pollock‐Tahiri, E., Yang, J., Park, Y. J., et al. (2021) · Molecular Metabolism · doi:10.1016/j.molmet.2021.101185 · Cited by 19 · see citing works
“Gdf15 has been suggested as a marker of muscle wasting after cardiovascular surgery [46,47], is secreted by skeletal muscle during exercise, and promotes lipolysis [48].”
BackgroundExercise/Resistance Training and Muscle Stem Cells
Fukada, S., & Nakamura, A. (2021) · Endocrinology and Metabolism · doi:10.3803/enm.2021.401 · Cited by 19 · see citing works
Silva-Bermúdez, L. S., Sevastyanova, T. N., Schmuttermaier, C., Torre, C. D. L., Schumacher, L., Klüter, H., & Kzhyshkowska, J. G. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.760577 · Cited by 18 · see citing works
“Recent data showed that GFRAL expression is also present in human adipocytes and prostate cancer cells (29, 30).”
BackgroundMyokines: Novel therapeutic targets for diabetic nephropathy
Yang, M., Luo, S., Yang, J., Chen, W., He, L., Liu, D., Zhao, L., & Wang, X. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.1014581 · Cited by 18 · see citing works
“Moreover, electrical stimulation induced the contraction of primary human muscle cells for 3 h and also induced the release of GDF15 into the culture medium (112).”
BackgroundSabaratnam, R., Kristensen, J. M., Pedersen, A. J. T., Kruse, R., Handberg, A., Wojtaszewski, J. F. P., & Højlund, K. (2024) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgae032 · Cited by 18 · see citing works
Endocrine Mechanisms Connecting Exercise to Brown Adipose Tissue Metabolism: a Human Perspective
Méndez-Gutiérrez, A., Osuna‐Prieto, F. J., Aguilera, C. M., Ruiz, J. R., & Sánchez‐Delgado, G. (2020) · Current Diabetes Reports · doi:10.1007/s11892-020-01319-7 · Cited by 18 · see citing works
“liver, it is also expressed, among others, in the skeletal muscle, WAT, and BAT [46, 47].”
BackgroundRegulation of diurnal energy balance by mitokines
Klaus, S., Gil, C. I., & Ost, M. (2021) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-020-03748-9 · Cited by 17 · see citing works
Fiorenza, M., Checa, A., Sandsdal, R. M., Jensen, S. B. K., Juhl, C. R., Noer, M. H., Bogh, N. P., Lundgren, J. R., Janus, C., Stallknecht, B. M., et al. (2024) · Cell Reports Medicine · doi:10.1016/j.xcrm.2024.101629 · Cited by 14 · see citing works
“11,12 15–17 Expression of FGF21 and GDF15 is regulated by the same molecular pathway, namely the integrated stress response, which is activated by a variety of cellular stresses.”
CHOP is dispensable for exercise-induced increases in GDF15
Townsend, L. K., Medak, K. D., Weber, A. J., Dibe, H. A., Shamshoum, H., & Wright, D. C. (2021) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00698.2021 · Cited by 15 · see citing works
Aerobic exercise and lipolysis: A review of the β-adrenergic signaling pathways in adipose tissue
Rodrigues, A. C., Prímola‐Gomes, T. N., Pelúzio, M. D. C. G., Hermsdorff, H. H. M., & Natali, A. J. (2020) · Science & Sports · doi:10.1016/j.scispo.2020.04.006 · Cited by 16 · see citing works
Mimicking exercise in vitro: effects of myotube contractions and mechanical stretch on omics
Lautaoja-Kivipelto, J. H., Turner, D. C., Sharples, A. P., Kivelä, R., Pekkala, S., Hulmi, J. J., & Ylä‐Outinen, L. (2023) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00586.2022 · Cited by 14 · see citing works
Poor Appetite & Aging: The Role of Physical Activity under a Geroscience Perspective
Barreto, P. D. S. (2022) · The journal of nutrition health & aging · doi:10.1007/s12603-022-1849-x · Cited by 14 · see citing works
“GDF15 may be considered as an exerkine, since it is secreted by the muscle during exercise (23).”
BackgroundThe search for systemic biomarkers for monitoring degenerative lumbar spinal disorders
Tarabeih, N., Shalata, A., Higla, O., Kalinkovich, A., & Livshits, G. (2022) · Osteoarthritis and Cartilage Open · doi:10.1016/j.ocarto.2022.100323 · Cited by 13 · see citing works
Huang, Q., Monzel, A. S., Rausser, S., Haahr, R., Indik, C. E., Savin, M. J., Bobba‐Alves, N., Liu, C. C., Devine, J., Thompson, E., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.04.19.590241 · Cited by 13 · see citing works
Cancer cachexia: A tumor-driven disorder of whole-body homeostasis
Zhang, Y., Nipp, R. D., Janowitz, T., Li, Y.-P., D, D. C. G., & Li, M. (2026) · Cancer Cell · doi:10.1016/j.ccell.2026.03.012 · Cited by 13 · see citing works
“29–31 Many systemic effects are mediated through the canonical GFRAL pathway, linking central appetite regulation to whole-body metabolic adaptation.”
The different effects of intramuscularly-injected lactate on white and brown adipose tissue in vivo
Qu, Y., Chen, S., Zhou, L., Chen, M., Li, L., Ni, Y., & Sun, J. (2022) · Molecular Biology Reports · doi:10.1007/s11033-022-07672-y · Cited by 12 · see citing works
“Exercise ameliorates metabolic health, promotes lipolysis, and prevents the complications of obesity and type 2 diabetes [1, 2].”
BackgroundGDF15 mediates renal cell plasticity in response to potassium depletion in mice
Lasaad, S., Walter, C., Rafael, C., Morla, L., Doucet, A., Picard, N., Blanchard, A., Fromes, Y., Matot, B., Crambert, G., et al. (2023) · Acta Physiologica · doi:10.1111/apha.14046 · Cited by 12 · see citing works
Genome-wide analysis of a cellular exercise model based on electrical pulse stimulation
Lee, B., Kim, S., Shin, Y. J., Son, Y. H., Yang, J. W., Lee, S.-M., Yang, Y. R., Lee, K., & Kwon, K. (2022) · Scientific Reports · doi:10.1038/s41598-022-25758-2 · Cited by 11 · see citing works
“Studies involving organ-to-muscle communication by co-culturing muscle cells with other cell types 55 and using EPS-conditioned medium 56–58 have been conducted to address these differences.”
Katz, D. H., Lindholm, M. E., & Ashley, E. A. (2024) · Physiology · doi:10.1152/physiol.00024.2024 · Cited by 12 · see citing works
Abubaker, J. A., Abu‐Farha, M., Albatineh, A. N., Al‐Khairi, I., Cherian, P., Ali, H., Taher, I., Alajmi, F., Qaddoumi, M., Abdul‐Ghani, M. A., et al. (2025) · Biomedicines · doi:10.3390/biomedicines13071589 · Cited by 10 · see citing works
“A similar effect has been observed with high-and moderate-intensity exercise [21,22].”
Jachim, S. K., Sakamoto, A. E., Zhang, X., Pearsall, V. M., Schafer, M. J., & LeBrasseur, N. K. (2020) · Ageing Research Reviews · doi:10.1016/j.arr.2020.101147 · Cited by 10 · see citing works
“, 2019), GDF15 (Conte et al., 2020; Laurens et al., 2020), GPLD1 (Horowitz et al.”
InfluentialWen, B., Tang, R., Tang, S., Sun, Y., Xu, J., Zhao, D., Wang, T., & Yan, C. (2024) · Journal of Human Genetics · doi:10.1038/s10038-023-01216-3 · Cited by 9 · see citing works
Nintou, E., Karligiotou, E., Vliora, M., Ioannou, L. G., & Flouris, A. D. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232113446 · Cited by 9 · see citing works
“Published studies have used electrical pulse stimulation to induce acute [16–19] and chronic [20,21] exercise; aerobic [22], endurance [19,23], and resistance training [24]; and high-intensity [25] and moderate activity [26].”
BackgroundInfluentialRelevance of GDF15 as a biomarker for clinical outcomes after bariatric surgery
Urones, P., Juiz-Valiña, P., Outeiriño-Blanco, E., García-Brao, M. J., Barreiro, V. B., Cordido, F., & Sangiao‐Alvarellos, S. (2025) · Journal of Endocrinology · doi:10.1530/joe-25-0010 · Cited by 8 · see citing works
The role of GDF15 in food intake and appetitive behaviour
Cimino, I., & Coll, A. P. (2021) · Current Opinion in Endocrine and Metabolic Research · doi:10.1016/j.coemr.2021.100299 · Cited by 8 · see citing works
GDF15 is dispensable for the insulin-sensitizing effects of chronic exercise
Labour, A., Lac, M., Frassin, L., Lair, B., Murphy, E. E., Maslo, C., Monbrun, L., Calmy, M.-L., Marqués, M.-A., Viguerie, N., et al. (2024) · Cell Reports · doi:10.1016/j.celrep.2024.114577 · Cited by 8 · see citing works
Self-citationGDF15 is required for maintaining subcutaneous adipose tissue lipid metabolic signature
Igual-Gil, C., Bishop, C. A., Jähnert, M., Johann, K., Coleman, V., Baum, V., Kruse, M., Pfeiffer, A. F. H., Pivovarova‐Ramich, O., Ost, M., et al. (2024) · Scientific Reports · doi:10.1038/s41598-024-77448-w · Cited by 8 · see citing works
Rao, Z., Geng, X. H., Huang, P., Wei, Q., Liu, S., Qu, C., & Zhao, J. (2024) · Experimental Physiology · doi:10.1113/ep092319 · Cited by 6 · see citing works
“A recent study reported that GDF15 increased rapidly in response to muscle contraction (Laurens et al., 2020).”
Skeletal muscle growth to combat diabetes and obesity: the potential role of muscle‐secreted factors
Sammut, M. J., Thorne, B. R., & Melling, C. W. J. (2025) · Obesity · doi:10.1002/oby.24223 · Cited by 7 · see citing works
“Furthermore, the GDF15-rich conditioned media collected from contracting SkM cells increases lipolysis in adipocytes via GDNF family receptor α -like (GFRAL)/rearranged during transfection (RET) receptors, which was prevented following treatment with anti-GDF15 antibodies [45].”
Growth differentiation factor 15 as a potential diagnostic biomarker for rheumatoid arthritis
Liu, X., Essien, A. E., Lu, W., Jin, H., Pan, L., Li, Y., & Xiao, W. (2025) · Bone and Joint Research · doi:10.1302/2046-3758.145.bjr-2024-0230.r2 · Cited by 6 · see citing works
“40,44 For instance, Wang et al 45 reported increased serum GDF-15 in patients with cardiovascular disease, indicating its potential utility in detecting myocardial infarction and predicting mortality.”
Exerkines: Benign adaptation for exercise and benefits for non-alcoholic fatty liver disease
Chen, Y., Zhang, Y., Jin, X., Hong, S., & Tian, H. (2024) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2024.150305 · Cited by 5 · see citing works
Pancreatic cancer cachexia: A systemic consequence of multi-organ interactions
Xiao, A., Feng, Y., Yin, B., Zhang, J., Cao, Z., Liu, X., Liang, Y., & Wu, W. (2025) · hLife · doi:10.1016/j.hlife.2025.05.002 · Cited by 6 · see citing works
Exercise as elixir to combat cardiovascular ageing
Feng, Z., Yuan, X., Yi, W., Gao, F., Sun, Y., & Zhang, X. (2025) · Ageing Research Reviews · doi:10.1016/j.arr.2025.102848 · Cited by 5 · see citing works
What Is the Potential Relevance of Growth and Differentiation Factor-15 in Neurologic Disease?
Benarroch, E. E. (2025) · Neurology · doi:10.1212/wnl.0000000000214131 · Cited by 5 · see citing works
Schmid, A., Wilfurth, E., Höpfinger, A., Behrendt, M., Islami, E., Karrasch, T., Berghoff, M., & Schäffler, A. (2025) · Scientific Reports · doi:10.1038/s41598-025-14846-8 · Cited by 5 · see citing works
Adipose Tissue Lipid Metabolism During Exercise
Horowitz, J. F. (2022) · Physiology in health and disease · doi:10.1007/978-3-030-94305-9_7 · Cited by 5 · see citing works
The role of tissue oxygenation in obesity-related cardiometabolic complications
Li, G., Meex, R. C. R., & Goossens, G. H. (2024) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-024-09910-z · Cited by 5 · see citing works
Giannakogeorgou, A., KAHL, S., Granata, C., Heilmann, G., Mastrototaro, L., Dewidar, B., Bobrov, P., Esposito, I., Yavas, A., Trenkamp, S., et al. (2025) · Metabolism · doi:10.1016/j.metabol.2025.156391 · Cited by 4 · see citing works
Translating In Vitro Models of Exercise in Human Muscle Cells: A Mitocentric View
Yeo, R. X., Noone, J., & Sparks, L. M. (2023) · Exercise and Sport Sciences Reviews · doi:10.1249/jes.0000000000000330 · Cited by 4 · see citing works
Lunde, N. N., Osoble, N. M. M., Dalmao‐Fernández, A., Antobreh, A. S., Jafari, A., Singh, S. K., Nyman, T. A., Rustan, A. C., Solberg, R., & Thoresen, G. H. (2023) · Biomedicines · doi:10.3390/biomedicines11112908 · Cited by 3 · see citing works
“This approach has previously been used to explore changes in, e.g., lipolysis and gene expression induced by conditioned medium given to the acceptor cells [30,31].”
MethodMarques, S. S., Liebaug, A., Maurer, S., Rothenbacher, D., Brenner, R. E., & Riegger, J. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.04.10.588843 · Cited by 3 · see citing works
James, E., Frampton, J., Murphy, K. G., & Chambers, E. S. (2025) · Journal of the Endocrine Society · doi:10.1210/jendso/bvaf013 · Cited by 2 · see citing works
“A limitation of previous studies examining the impact of acute exercise on GDF-15 release is the absence of a time-matched, resting control arm [3, 4, 7, 8]; thus exercise-induced changes cannot be distinguished from possible diurnal secretory responses [25].”
Sun, Y., Tang, S., Jingwei, L., Bing, W., Xu, J., Busu, L., Zhao, B. T., Ji, K., & Yan, C. (2025) · Orphanet Journal of Rare Diseases · doi:10.1186/s13023-025-03651-1 · Cited by 2 · see citing works
“Additionally, GDF15 binds to the glial cell line-derived neurotrophic factor receptor alpha-like (GFRAL) receptor, which interacts with its tyrosine kinase coreceptor rear-ranged during transfection (RET) to initiate a signaling cascade that may activate various intracellular pathways [7].”
Exercise Suppresses Appetite in Obesity: A Biochemical, Metabolic, and Molecular Approach
Razi, O., Zamani, N., de Moraes, C., Laher, I., & Hadjicharalambous, M. (2025) · Applied Sciences · doi:10.3390/app15116191 · Cited by 4 · see citing works
- 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 › Rheumatology › GDF15 and Related Biomarkers
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Health Sciences › Medicine › Rehabilitation › 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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