Myokine/Adipokine response to “Aerobic” exercise: Is it just a matter of exercise load?
Open accessAbstract
Purpose: Exercise health benefits are partly mediated by exertional changes in several myokines/adipokines. but little is known on individual variability, which is an important question in the context of personalized exercise prescription. This study aimed to compare the acute response of some of these biomarkers to aerobic exercise performed at the intensity corresponding to the maximum fat oxidation rate (FATmax) or the ‘anaerobic’ threshold (AT). Methods: Following a cross-over, counterbalanced design, 14 healthy untrained men (23±1 years) performed a 45-minute exercise bout at their FATmax or AT intensity (been previously determined through incremental exercise tests). The concentration of interleukin (IL)-15, follistatin, myostatin, fibroblast-growth factor (FGF)-21, irisin, resistin and omentin was measured at baseline and 0, 1, 3, 24, 48 and 72 hours post-exercise. Results: AT exercise was performed at a higher intensity (85±8 vs 52±14% of maximal oxygen uptake [VO2max], p0.05). Conclusion: In summary, Iincreasing exercise intensity load (from FATmax to AT) maximizes results in a higher response of the FGF-21, follistatin and omentin response to aerobic exercise, with the subsequent potential cardiometabolic benefits. No intensity effects were, however, observed on the remainder of biomarkers. or on the rate of responsiveness. Future research should address if manipulating other exercise variables (e.g., type, frequency) can promote a higher myokine/adipokine individual responsivenessresponse.
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An intensity-dependent increase in levels of FGF21 and follistatin in healthy untrained adults subjected to a 45-min treadmill challenge has been recently described.
“Indeed, an intensity-dependent increase in the levels of FGF21 and follistatin in healthy untrained adults subjected to a 45-min treadmill challenge has been recently described [285].”
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“In agreement with our findings, no changes in plasma levels of IL-15 were observed after 1 (Chan, 2004) or 3 h of cycling exercise (Rinnov et al., 2014), or after 2.”
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“…to induce cardiometabolic benefits through promoting the browning of white adipose tissue (WAT), and enhancing glucose homeostasis (Busquets et al., 2006; Nielsen et al., 2008; Elbelt et al., 2013; Kim H. J. et al., 2013; Woo et al., 2013; Fisher and Maratos-Flier, 2016; Perakakis et al., 2017).”
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“In line with these results, 12 weeks of aerobic exercise have proven superior to other types of exercise (i.e., resistance exercise and a combination of both resistance and aerobic exercise) for the promotion of omentin production in diabetic animals (de Castro et al., 2019).”
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Metabolic Health—The Role of Adipo-Myokines
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Effects of exercise intensity on white adipose tissue browning and its regulatory signals in mice
Tanimura, R., Kobayashi, L., Shirai, T., & Takemasa, T. (2022) · Physiological Reports · doi:10.14814/phy2.15205 · Cited by 36 · see citing works
“Previous studies have reported that a higher intensity endurance exercise induced higher response of FGF21 in humans (He et al., 2019).”
BackgroundHepatokines as a Molecular Transducer of Exercise
Seo, D. Y., Park, S.-H., Marquez, J. C., Kwak, H., Kim, T. N., Bae, J. H., Koh, J., & Han, J. (2021) · Journal of Clinical Medicine · doi:10.3390/jcm10030385 · Cited by 36 · see citing works
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Effects of Maternal Exercise Modes on Glucose and Lipid Metabolism in Offspring Stem Cells
Jevtovic, F., Zheng, D., Houmard, J. A., Krassovskaia, P. M., Lopez, C. A., Wisseman, B., Steen, D. M., Broskey, N. T., Isler, C. M., DeVente, J., et al. (2023) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgad059 · Cited by 33 · see citing works
Delfan, M., Saeidi, A., Supriya, R., Escobar, K. A., Laher, I., Heinrich, K. M., Weiss, K., Knechtle, B., & Zouhal, H. (2024) · Nutrition & Metabolism · doi:10.1186/s12986-024-00785-0 · Cited by 31 · see citing works
“Other studies report increases in in irisin concentrations following high-intensity exercise, albeit with a limited focus on the implications of HIIT [72, 75, 76].”
BackgroundMéndez-Gutiérrez, A., Aguilera, C. M., Osuna‐Prieto, F. J., Martínez‐Téllez, B., Rico-Prados, M. C., Acosta, F. M., Elvira, J. M. L., Ruiz, J. R., & Sánchez‐Delgado, G. (2022) · European Journal of Sport Science · doi:10.1080/17461391.2022.2040597 · Cited by 25 · see citing works
“Previous studies in middle-aged and young adults observed increases in plasma levels of ANP (Peres et al., 2018), follistatin (He et al., 2019), and meteorin-like (Saghebjoo, Einaloo, Mogharnasi, & Ahmadabadi, 2018) after a session of moderate-intensity endurance exercise between 40 and 60 min of…”
BackgroundResultInfluentialOuerghi, N., Fradj, M. K. B., Duclos, M., Bouassida, A., Feki, M., Weiss, K., & Knechtle, B. (2022) · Biology · doi:10.3390/biology11060853 · Cited by 21 · see citing works
Individual Responsiveness to Physical Exercise Intervention in Acutely Hospitalized Older Adults
Valenzuela, P. L., Ortiz-Alonso, J., Bustamante-Ara, N. E., Vidán, M. T., Rodríguez‐Romo, G., Mayordomo‐Cava, J., Javier-González, M., Hidalgo-Gamarra, M., Lopéz-Tatis, M., Valadés-Malagón, M. I., et al. (2020) · Journal of Clinical Medicine · doi:10.3390/jcm9030797 · Cited by 19 · 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
Vasyukova, O. V., Kasyanova, Y. V., Okorokov, P. L., & Bezlepkina, O. B. (2021) · Problems of Endocrinology · doi:10.14341/probl12779 · Cited by 18 · see citing works
The production, detection, and origin of irisin and its effect on bone cells
Zhong, X., Sun, X., Shan, M., Zhao, X., Zhang, R., Zhao, Y., & Yang, Q. (2021) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2021.02.181 · Cited by 17 · see citing works
Current knowledge and scientific trends in myokines and exercise research in the context of obesity
Letukienė, A., Hendrixson, V., & Ginevičienė, V. (2024) · Frontiers in Medicine · doi:10.3389/fmed.2024.1421962 · Cited by 16 · see citing works
“…for activating the function of other stimuli, for example, those involving intracellular and extracellular signaling pathways, and the stimulus effect is observed not only in muscles but also in other organs or tissues (including adipose tissue, the liver, the brain, etc.) (7, 10, 13, 14, 16).”
BackgroundMiazgowski, T., Miazgowski, B., Kaczmarkiewicz, A., & Kopec, J. A. (2021) · Archives of Endocrinology and Metabolism · doi:10.20945/2359-3997000000333 · Cited by 14 · see citing works
Cosio, P. L., Peláez, M., Cadefau, J. A., & Farrán-Codina, A. (2022) · Biological Research For Nursing · doi:10.1177/10998004221142580 · Cited by 13 · see citing works
“…using their first (Daskalopoulou et al., 2014; Norheim et al., 2014; Qiu et al., 2018; Tsuchiya et al., 2014; 2015), second (Dror et al., 2022; He et al., 2018; 2019; Lagzdina et al., 2020; Nygaard et al., 2015) or third (Tsai et al., 2021) generation kits, although Shanghai Sunred Biological…”
BackgroundMethodInfluentialHekmatikar, A. A., Nelson, A., & Petersen, A. C. (2023) · BMC Cancer · doi:10.1186/s12885-023-11391-3 · Cited by 13 · see citing works
Jürimäe, J., Vaiksaar, S., Purge, P., & Tillmann, V. (2021) · Frontiers in Physiology · doi:10.3389/fphys.2021.689696 · Cited by 12 · see citing works
“Specifically, higher exercise load at the intensity of AnT (total EE of 762 ± 118 kcal.h−1) produced significantly higher postexercise FGF-21 response in comparison with a lower exercise load at the intensity of maximum fat oxidation rate (total EE of 480 ± 160 kcal.h−1; He et al., 2019).”
BackgroundResultInfluentialLim, J. Y., & Kim, E. (2023) · Metabolites · doi:10.3390/metabo13090979 · Cited by 13 · see citing works
Exercise, Exerkines, and Sarcopenia
Chung, H. S., & Choi, K. M. (2026) · Diabetes & Metabolism Journal · doi:10.4093/dmj.2025.0972 · Cited by 12 · see citing works
“Similarly, He et al. [64] reported that the magnitudes of FGF-21 and follistatin responses were significantly elevated with higher aerobic exercise intensity.”
Contribution of organokines in the development of NAFLD/NASH associated hepatocellular carcinoma
Vachher, M., Bansal, S., Kumar, B., Yadav, S., Arora, T. K., Wali, N. M., & Burman, A. (2022) · Journal of Cellular Biochemistry · doi:10.1002/jcb.30252 · Cited by 11 · see citing works
Newman, J. E., King, I., Flemming, N., Broadhouse, K. M., Buhmann, R., Rose, G. L., Jenkins, D. G., Askew, C. D., & Schaumberg, M. A. (2025) · Experimental Gerontology · doi:10.1016/j.exger.2025.112850 · Cited by 10 · see citing works
“Basal circulating plasma levels of irisin concentrations have also been shown to be lower in older (versus young) (Ye et al., 2019) and physically active (versus sedentary) participants (He et al., 2019).”
Second Ventilatory Threshold Assessed by Heart Rate Variability in a Multiple Shuttle Run Test
Stergiopoulos, D. C., Kounalakis, S. N., Miliotis, P. G., & Geladas, N. D. (2020) · International Journal of Sports Medicine · doi:10.1055/a-1214-6309 · Cited by 10 · see citing works
Effects of a One-week Vacation with Various Activity Programs on Metabolism and Adipokines
Neumayr, G., Engler, C., Lunger, L., & Lechleitner, P. (2020) · International Journal of Sports Medicine · doi:10.1055/a-1297-4669 · Cited by 10 · see citing works
Physical Exercise-Induced FGF-21 to Fight Obesity: An Update Review
Vecchiatto, B., de Castro, T. L., Muller, C. R., Azevedo‐Martins, A. K., & Evangelista, F. S. (2022) · Obesities · doi:10.3390/obesities2040031 · Cited by 9 · see citing works
“(2019) [45] that showed a higher serum concentration of FGF-21 after performing exercise at 90% of maximum heart rate (HR max) in comparison to an exercise performed at 69% of HR max.”
BackgroundInfluentialSupriya, R., Shishvan, S. R., Kefayati, M., Abednatanzi, H., Razi, O., Bagheri, R., Escobar, K. A., Pashaei, Z., Saeidi, A., Shahrbanian, S., et al. (2023) · Nutrients · doi:10.3390/nu15224803 · Cited by 8 · see citing works
“The effect of aerobic or resistance training on omentin-1 is conflicting, with studies showing increased levels [64,65] or unchanged levels [60].”
BackgroundAcute physical exercise and ambulatory blood pressure in resistant hypertension
Saco‐Ledo, G., Valenzuela, P. L., Almazán-Polo, J., Plaza‐Florido, A., Alejo, L. B., Bustos, A., Río-García, A., Gálvez, B. G., Rubio-González, E., Fiuza‐Luces, C., et al. (2024) · Journal of Hypertension · doi:10.1097/hjh.0000000000003924 · Cited by 7 · see citing works
Kowalik, S., Wiśniewska, A., Kędzierski, W., & Janczarek, I. (2020) · Animals · doi:10.3390/ani10122268 · Cited by 6 · see citing works
Myokines in obese adolescents with aerobic exercise
Kasyanova, Y. V., Vasyukova, O. V., Okorokov, P. L., Zuraeva, Z. T., & Bezlepkina, O. B. (2022) · Problems of Endocrinology · doi:10.14341/probl13138 · Cited by 6 · see citing works
PRASAD, V. V., Samson, J. S., & Parvathi, V. D. (2024) · Biocell · doi:10.32604/biocell.2024.048776 · Cited by 6 · see citing works
Healthy adipose tissue after menopause: contribution of balanced diet and physical exercise
Vecchiatto, B., de Castro, T. L., Ferreira, N. J. R., & Evangelista, F. S. (2025) · Exploration of Endocrine and Metabolic Diseases · doi:10.37349/eemd.2025.101424 · Cited by 5 · see citing works
Shen, F., Zhao, Y. X., Ding, W., Liu, K., Ren, X., Zhang, Q., Yu, J., Hu, Y., Zuo, H., Guo, M., et al. (2020) · Life Sciences · doi:10.1016/j.lfs.2020.118786 · Cited by 5 · see citing works
Więcek, M., Mardyła, M., Szymura, J., Kantorowicz, M., Kuśmierczyk, J., Maciejczyk, M., & Szyguła, Z. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26010350 · Cited by 4 · see citing works
“These authors noted a decrease in resistin after a single strength training session in obese men, as well as some data by confirming a decrease following a 45 min exercise intervention (85% VO 2 max) in healthy young men [56,57].”
Shiomitsu, S., Hansen, C. M., Lenfest, M. I., Frye, C. W., & Wakshlag, J. J. (2022) · Journal of the American Veterinary Medical Association · doi:10.2460/javma.22.07.0323 · Cited by 4 · see citing works
Exerkine response to acute exercise: Still much to discover
Valenzuela, P. L., Rivas-Baeza, B., Fiuza‐Luces, C., & Lucía, A. (2024) · Journal of sport and health science/Journal of Sport and Health Science · doi:10.1016/j.jshs.2024.04.007 · Cited by 3 · see citing works
“He et al. 15 reported that the magnitude of the FGF-21 or follistatin response increased with the intensity of acute aerobic exercise (i.e., from » 52% to » 85% of maximal oxygen uptake).”
BackgroundExercise in rehabilitation of patients with breast cancer
Владимировна, Б. И., Vitsenya, M. V., Ageev, F. T., & Вачиковна, П. Н. (2022) · Russian Cardiology Bulletin · doi:10.17116/cardiobulletin20221704116 · Cited by 2 · see citing works
Cao, W., Gu, Z., Fu, R. G., Chen, Y., He, Y., Rui, Y., Yang, X., & He, Z. (2025) · Genes · doi:10.3390/genes16070810 · Cited by 1 · see citing works
“We also observed increased serum follistatin post-exercise (overall and in men, especially Hill/Running), consistent with some studies linking it to exercise stress or muscle recruitment [55–57].”
Exercise Intensity and Circulating Exerkine Responses: A Narrative Review of Selected Molecules
Zhao, Y., Wang, T., Zhang, X., Wang, W., Fu, Y., Laher, I., & Li, S. (2026) · Biomolecules · doi:10.3390/biom16060852 · Cited by 1 · see citing works
“[71].”
Hejazi, K., Rahimi, G. R. M., Saeidi, A., Ayed, K., Laher, I., Coso, J. D., Hackney, A. C., Granacher, U., & Zouhal, H. (2026) · Sports Medicine · doi:10.1007/s40279-026-02446-z · Cited by 1 · see citing works
“Various myokines have been proposed to mediate train-ing-induced changes in energy expenditure [11], with irisin being studied extensively [12].”
Newman, J. E., Jenkins, D. G., Mielke, G. I., Askew, C. D., & Schaumberg, M. A. (2023) · Journal of Clinical Exercise Physiology · doi:10.31189/2165-6193-12.4.111 · Cited by 1 · see citing works
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EXERCISE AND HEALTHY LIFE EXPECTANCY
Hagiu, B.-A. (2021) · The Annals of Dunarea de Jos University of Galati Fascicle XV Physical Education and Sport Management · doi:10.35219/efms.2021.2.01
“hours after exertion the situation is reversed (He et al, 2019 – [12]).”
BackgroundBelastung, Muskelreparatur, Muskelremodulation, Immunsystem
Laube, W. (2023) · Springer eBooks · doi:10.1007/978-3-662-67753-7_11
Cross-talk between hepatokines as Liver indused-exercise factors and organokinesPreprint
Rad, R. S. (2023) · Research Square · doi:10.21203/rs.3.rs-3734627/v1
Role of Myokines and prospects for their role in Diabetes Mellitus Therapy
Nuriya, K., Farida, M., Sharma, R., Liliya, S., Mkhitaryan, X. E., Chergizova, B., Salikhova, Y., Niyazova, Y., Ryspayeva, G., Evnevich, A., et al. (2024) · Research Journal of Pharmacy and Technology · doi:10.52711/0974-360x.2024.00786
Comparison of Muscle Damage Markers and Myokines between Adult and Middle-Aged Marathon Runners
Zocoler, C. A. S., Sierra, A., Lima, G. H. O., Galán, B. S. M., Barbeiro, H. V., de Souza, H. P., & Cury‐Boaventura, M. F. (2025) · OBM Geriatrics · doi:10.21926/obm.geriatr.2501301
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“FGF21 has recently been identified as an exercise-responsive factor, with circulating levels increasing after endurance exercise [7,8].”
Hogan, C. M., Cross, T. J., Tiong, M. J., Pratheepan, P., Blaxland, A., Machan, E. A., & Rooney, K. (2026) · Medicine & Science in Sports & Exercise · doi:10.1249/mss.0000000000004027
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Combined kinesiotherapy in the rehabilitation of osteoarthritis patients after COVID-19
Voloshyna, O. B., Балашова, І. В., Lysyi, I. S., Дукова, О. Р., & Ковальчук, Л. Я. (2026) · Physical rehabilitation and recreational health technologies · doi:10.15391/prrht.2026-11(4).03
- Authors
- He, Z., Tian, Y., Valenzuela, P. L., Huang, C., Zhao, J., Hong, P., He, Z., Yin, S., & Lucia, A.
- Affiliations
- China Institute of Sport Science (CN)
- General Administration of Sport of China (CN)
- Universidad de Alcalá (ES)
- Shandong Sport University (CN)
- Chinese People's Liberation Army (CN)
- Corresponding author
- Tian, Ye
- Venue
- Frontiers in Physiology
- Publisher
- Frontiers Media SA
- Published
- 2019-05-29
- Volume
- 10
- Pages
- 691-691
- ISSN
- 1664-042X (ISSN-L)
- PMC
- PMC6549222
- OpenAlex
- W2947053774
- Cited by
- 59
- References
- 65
- Citations by year
- 2026: 7 · 2025: 6 · 2024: 6 · 2023: 7 · 2022: 11 · 2021: 8 · 2020: 12 · 2019: 1 · 2018: 1
- FWCI
- 5.59
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Physiology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- ABACUS. Repositorio de Producción Científica (Universidad Europea) (submittedVersion, cc-by-nc-nd)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, other-oa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Ministerio de Ciencia, Innovación y Universidades (PI15/00558, PI18/00139)
- Universidad de Alcalá (FPI-2016)
- Topics
- Health Sciences › Medicine › Rehabilitation › Exercise and Physiological Responses
- Health Sciences › Medicine › Complementary and alternative medicine › Cardiovascular and exercise physiology
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- myokines, adipokines, aerobic exercise, exercise intensity, fat oxidation rate, anaerobic threshold, FGF21, follistatin, myostatin, irisin, resistin, omentin, IL-15, interindividual variability, acute exercise response, cardiometabolic health, individualized exercise prescription
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