Effect of Eight-week Selected Aerobic and Resistance Exercises on the Plasma Levels of Irisin, Follistatin, and Fibroblast Growth Factor 21 in Women Recovered from COVID-19

Document Type : Original Article


1 Islamic Azad University, Research Sciences Branch, Tehran.

2 Department of Exercise Physiology, Science and research Branch, Islamic Azad University, Tehran, Iran

3 Assistant Professor, Department of Infectious Diseases, University of Medical Sciences, Abadan, Iran

4 Assistant Professor, Department of Physiology, University of Medical Sciences, Abadan, Iran.

5 Associate Professor, Department of Physical Education and Sports Sciences, Science and Research Unit, Islamic Azad University, Tehran, Iran.



Background and Objectives Recently, performing regular sports activities has been considered an effective strategy for the rehabilitation of patients who have recovered from COVID-19. The present study aimed to assess the effect of eight weeks of selected aerobic and resistance exercises on the plasma levels of irisin, follistatin, and fibroblast growth factor 21 (FGF21) in women who recovered from COVID-19. Subjects and Methods A total of 33 women who recovered from COVID-19 were assigned to three groups, namely aerobic exercise, resistance, and control, after the general call and selection. Aerobic training with an intensity of 50%-70% of the reserve heart rate and resistance training with an intensity of 40%-75% of a maximum repetition was performed for eight weeks (three sessions per week). Irisin, follistatin, and FGF21 levels were measured using the ELISA method. The data were analyzed using the analysis of variance statistical test at the significant level of < 0.05. Results As illustrated by the results, selected aerobic and resistance exercises caused a significant increase in irisin, follistatin, and FGF21 levels. The results of the post hoc test demonstrated that this increase was significant in the aerobic and resistance groups compared to the control group. Moreover, within-group changes pointed to a significant increase in the mean before and after the intervention in the aerobic and resistance groups. Conclusion Carrying out selected aerobic and resistance exercises in women who recovered from COVID-19 boosts their physical strength and is effective in quick recovery by restoring some indicators of myokine profile.


Parisa Amiri Farsani [PumMed] [Google Scholar]

Farshad Ghazalian [PumMed] [Google Scholar]

 Sara Mobarak [PumMed] [Google Scholar]

 Esmat Radmanesh [PumMed] [Google Scholar]

 Mandana Gholami [PumMed] [Google Scholar]


[1] Gorskaya YF, Semenova EN, Nagurskaya EV, Bekhalo VA, Nesterenko VG. Apoptosis and P53 activation are involved in COVID-19 pathogenesis. COVID-19 Pandemic. 2021;2:208-13
[2] Bo W, Xi Y, Tian Z. The role of exercise in rehabilitation of discharged COVID-19 patients. Sports Medicine and Health Science. 2021;3(4):194–201. [DOI: 10.1016/j.smhs.2021.09. 001] [PMID]
[3] Gurovich AN, Tiwari S, Kehl S, Umucu E, Peñailillo L. A novel “Eccentric” therapeutic approach for individuals recovering from COVID-19. Cardiopulmonary Physical Therapy Journal. 2021;32:S15-21. [DOI: 10.1097/CPT.0000000000000163]
[4] Filgueira TO, Castoldi A, Santos LER, de Amorim GJ, de Sousa Fernandes MS, Anastácio WLDN, et al. The Relevance of a Physical Active Lifestyle and Physical Fitness on Immune Defense: Mitigating Disease Burden, With Focus on COVID-19 Consequences. Front Immunol. 2021;12:587146. [DOI: 10.3389/fimmu.2021.587146] [PMID] [PMCID]
[5] Yalçin M, Koçak E, Kacar M. The role of exercise as a treatment and preventive strategy during COVID-19 pandemic. Anatolian Clinic the Journal of Medical Sciences. 2020;25(Special Issue on COVID 19):238-45. [DOI: 10.21673/anadoluklin.731902]
[6] Nobari H, Fashi M, Eskandari A, Pérez-Gómez J, Suzuki K. Potential Improvement in Rehabilitation Quality of 2019 Novel Coronavirus by Isometric Training System; Is There “Muscle-Lung Cross-Talk”? International Journal of Environmental Research and Public Health. 2021;18(12):6304. [DOI: 10.3390/ijerph18126304]
[7] Piccirillo R. Exercise-Induced Myokines With Therapeutic Potential for Muscle Wasting. Front Physiol. 2019;10:287. [DOI: 10.3389/fphys.2019.00287] [PMID] [PMCID]
[8] De Sousa RAL, Improta-Caria AC, Aras-Júnior R, de Oliveira EM, Soci ÚPR, Cassilhas RC. Physical exercise effects on the brain during COVID-19 pandemic: links between mental and cardiovascular health. Neurol Sci. 2021;42(4):1325-34. [DOI: 10.1007/s10072-021-05082-9] [PMID] [PMCID]
[9] Aristizabal JP, Navegantes R, Melo E, Pereira A Jr. Use of Heart Rate Variability Biofeedback to Reduce the Psychological Burden of Frontline Healthcare Professionals Against COVID-19. Front Psychol. 2020;11:572191. [DOI 10.3389/fpsyg.2020. 572191] [PMID]
[10] Jimeno-Almazán A, Pallarés JG, Buendía-Romero Á, Martínez-Cava A, Franco-López F, Sánchez-Alcaraz Martínez BJ, et al. Post-COVID-19 Syndrome and the Potential Benefits of Exercise. Int J Environ Res Public Health. 2021;18(10):5329. [DOI: 10.3390/ijerph18105329] [PMID] [PMCID]
[11] Catalano A. COVID-19: Could irisin become the handyman myokine of the 21st century?. Coronaviruses. 2020;1(1):32-41. [DOI: 10.2174/2666796701999200617154655]
[12] Ghanei M, Shirvani H, Roshani Koosha MS, Shakibaee A, Arabzadeh E. Exercise training and muscle–lung crosstalk: The emerging roles of Irisin and Semaphorin-3A in pulmonary diseases. Journal of Exercise & Organ Cross Talk.2021;1(1):24-8. [DOI: 10.22034/JEOCT.2021.289682.1007]
[13] Ijiri N, Kanazawa H, Asai K, Watanabe T, Hirata K. Irisin, a newly discovered myokine, is a novel biomarker associated with
physical activity in patients with chronic obstructive pulmonary disease. Respirology. 2015;20(4):612-7. [DOI: 10.1111/resp.12513] [PMID]
[14] Benassi R, Da Silva DD, Da Silva Nogueira ER, Da Silva EP, De Oliveira JD, Da Silva Manhaes T, et al. Irisin and effects on cardiometabolic diseases in physical conditioning and treatment of covid-19. World Journal of Pharmacy and Pharmaceutical Sciences. 2021;10(2):76-87. [DOI: 10.20959/ wjpps20212-18172]
[15] Taheri F, Fathi M, Hejazi K. [The Effect of 10 Weeks Core Muscle Training on Levels of Follistatin, Myostatin, and Pain in Elderly Women. Quarterly of the Horizon of Medical Sciences (Persian)]. 2021;27(2):164-81. [DOI: 10.32598/hms.27.2.1970.12]
[16] Attarzadeh Hosseini SR, Motahari Rad M, Moien Neia N. [The effect of two different intensities resistance training on muscle growth regulatory myokines in sedentary young women (Persian)]. J Arak Uni Med Sci. 2016;19(7):56-65. [Link]
[17] Steenblock C, Schwarz PEH, Ludwig B, Linkermann A, Zimmet P, Kulebyakin K, et al. COVID-19 and metabolic disease: mechanisms and clinical management. Lancet Diabetes Endocrinol. 2021;9(11):786-98. [DOI: 10.1016/S2213-8587(21) 00244-8] [PMID] [PMCID]
[18] Yan J, Nie Y, Cao J, Luo M, Yan M, Chen Z, et al. The Roles and Pharmacological Effects of FGF21 in Preventing Aging-Associated Metabolic Diseases. Front Cardiovasc Med. 2021;8:655575. [DOI: 10.3389/fcvm.2021.655575] [PMID]
[19] Leal LG, Lopes MA, Batista ML Jr. Physical Exercise-Induced Myokines and Muscle-Adipose Tissue Crosstalk: A Review of Current Knowledge and the Implications for Health and Metabolic Diseases. Front Physiol. 2018;9:1307. [DOI: 10.3389/fphys.2018.01307] [PMID] [PMCID]
[20] Qi D, Yan X, Xiang J, Peng J, Yu Q, Tang X, et al. Effects of Early Physical and Pulmonary Rehabilitation for Severely and Critically ill COVID-19 Patients. Research Square. 2020; Vol (1): 1-17. [DOI: 10.21203/rs.3.rs-66798/v1]
[21] Brzycki M. Strength Testing-Predicting a One-Rep Max from Reps-Tofatigue. Journal of Physical Education, Recreation & Dance. 1993;64(1):88-90. [DOI: 10.1080/07303084.1993.10606684]
[22] Burtscher J, Millet G. P & Burtscher M. Low Cardiorespiratory and Mitochondrial Fitness as Risk Factors in Viral Infections: Implications for COVID-19. J Sports Med. 2021;55(8):413-5. [DOI: 10.1136/bjsports-2020-103572] [PMID]
[23] Leustean L, Preda C, Teodoriu L, Mihalache L, Arhire L, Ungureanu MC. Role of Irisin in Endocrine and Metabolic Disorders—Possible New Therapeutic Agent? Applied Sciences. 2021;11(12):5579. [DOI: 10.3390/app11125579]
[24] Amanat S, Sinaei E, Panji M, MohammadporHodki R, Bagheri-Hosseinabadi Z, Asadimehr H, et al. A Randomized Controlled Trial on the Effects of 12 Weeks of Aerobic, Resistance, and Combined Exercises Training on the Serum Levels of Nesfatin-1, Irisin-1 and HOMA-IR. Front Physiol. 2020;11:562895. [DOI: 10.3389/fphys.2020.562895] [PMID] [PMCID]
[25] Khosravianfar M, Jalali dehkordi K, Sharifi G, jalali dehkordi A. Comparison of the effect of period of resistance, aerobic and concurrent training on irisin, CRP serum levels in obese women. Journal of Shahrekord University Medical Sciences. 2018;20(2):13-23.
[26] Huh JY, Panagiotou G, Mougios V, Brinkoetter M, Vamvini MT,
Amiri Farsani, et al. Response of Plasma Levels of Selected Myokines to Aerobic and Resistance Exercises in Women Recovered from COVID-
19. JSMJ. 2024; 22(4):526-541
Journal of Medical Sciences
September & October 2024. Vol 22. No 4
Schneider BE, et al. FNDC5 and irisin in humans: I. Predictors of circulating concentrations in serum and plasma and II. mRNA expression and circulating concentrations in response to weight loss and exercise. Metabolism. 2012;61(12):1725-38. [DOI: 10.1016/j.metabol.2012.09.002] [PMID] [PMCID]
[27] Nazar Ali P, Ansari Ghadim R, Rahmani H. [The effect of high-intensity circular exercises on high serpentine serum levels and insulin resistance in inactive women with overweight (Persian)]. J Endocrine Metabol Iran. 2018;10(40):149-62. [DOI: 10.22089/spj.2019.6823.1852]
[28] Nigro E, Polito R, Alfieri A, Mancini A, Imperlini E, Elce A, et al. Molecular mechanisms involved in the positive effects of physical activity on coping with COVID-19. Eur J Appl Physiol. 2020;120(12):2569-82. [DOI: 10.1007/s00421-020-04484-5] [PMID] [PMCID]
[29] Dianatinasab A, Koroni R, Bahramian M, Bagheri-Hosseinabadi Z, Vaismoradi M, Fararouei M, et al. The effects of aerobic, resistance, and combined exercises on the plasma irisin levels, HOMA-IR, and lipid profiles in women with metabolic syndrome. J Exerc Sci Fit. 2020;18(3):168-76. [DOI: 10.1016/ j.jesf.2020.06.004] [PMID]
[30] Huh JY, Dincer F, Mesfum E, Mantzoros CS. Irisin stimulates muscle growth-related genes and regulates adipocyte differentiation and metabolism in humans. Int J Obes (Lond). 2014;38(12):1538-44. [DOI: 10.1038/ijo.2014.42] [PMID]
[31] Norheim F, Langleite TM, Hjorth M, Holen T, Kielland A, Stadheim HK, Gulseth HL, Birkeland KI, Jensen J, Drevon CA. The effects of acute and chronic exercise on PGC-1α, irisin and browning of subcutaneous adipose tissue in humans. FEBS J. 2014;281(3):739-49. [DOI: 10.1111/febs.12619] [PMID]
[32] Aghabagi E, Ghanbar Zadeh M, Ranjbar R. The effect of 8 weeks endurance and resistance training on Myostatin and Follistatin serum level in postmenopausal women's. Journal of Advanced Pharmacy Education & Research. 2020;10(S4): 63–9. [Link]
[33] Shirzad J, Tofighi A, Tolouei Azar J & Khadem Ansari M. H. [Adaptation of Irisin, Follistatin and Myostatin to 8 Weeks of Resistance, Endurance and Concurrent Training in Obese Men (Persian)]. Sport Physiology & Management Mnvestigations. 2021;12(4):23-41. [Link]
[34] Moosavi R, Kazemi F, Nazarali P. [Effect of a period of total body resistance training (TRX) on serum myostatin and follistatin concentrations in inactive women (Persian)]. Journal of Sabzevar University of Medical Sciences. 2021;28(1):41-7. [Link]
[35] Motevalli MS, Dalbo VJ, Attarzadeh RS, Rashidlamir A, Tucker PS, Scanlan AT. The effect of rate of weight reduction on serum myostatin and follistatin concentrations in competitive wrestlers. Int J Sports Physiol Perform. 2015;10(2):139-46. [DOI: 10.1123/ijspp.2013-0475] [PMID]
[36] Chapman MA, Arif M, Emanuelsson EB, Reitzner SM, Lindholm ME, Mardinoglu A, Sundberg CJ. Skeletal Muscle Transcriptomic Comparison between Long-Term Trained and Untrained Men and Women. Cell Rep. 2020;31(12):107808. [DOI: 10.1016/j.celrep.2020.107808] [PMID]
[37] McPherron AC, Lawler AM, Lee SJ. Regulation of skeletal muscle mass in mice by a new TGF-beta superfamily member. Nature. 1997;387(6628):83-90. [DOI: 10.1038/387083a0] [PMID]
[38] Domin R, Dadej D, Pytka M, Zybek-Kocik A, RuchaƂa M, Guzik P.
Effect of Various Exercise Regimens on Selected Exercise-Induced Cytokines in Healthy People. Int J Environ Res Public Health. 2021;18(3):1261. [DOI: 10.3390/ijerph18031261] [PMID] [PMCID]
[39] El Assar M, Álvarez-Bustos A, Sosa P, Angulo J, Rodríguez-Mañas L. Effect of Physical Activity/Exercise on Oxidative Stress and Inflammation in Muscle and Vascular Aging. Int J Mol Sci. 2022;23(15):8713. [DOI: 10.3390/ijms23158713] [PMID] [PMCID]
[40] AbdelMassih AF, Menshawey R, Hozaien R, Kamel A, Mishriky F, Husseiny R, et al. The potential use of lactate blockers for the prevention of COVID-19 worst outcome, insights from exercise immunology. Med Hypotheses. 2021;148:110520. [DOI: 10.1016/j.mehy.2021.110520] [PMID]
[41] Kolali A, Radfar B. Khayami K, Khayami H. The effect of spirulina supplement along with aerobic exercise on the changes of myostatin, follistatin and fat mass of overweight middle-aged peopl. Gorgan The 5th National Sports Physiology and Biochemistry Conference. 2020. [Link]
[42] Esazadeh L, Hosseini Kakhk A, Khajeie R, Hejazi S. M. The Effect of Concurrent Training Order (Resistance-Aerobic) on Some Factors of Physical Fitness, Functional Capacity and Serum Levels of Myostatin and Follistatin Hormones in Postmenopausal Women (Clinical Trial). Journal of Sport Biosciences. 2020;12(2):189-206. [DOI: 10.22059/jsb.2020. 282311.1345]
[43] Gaich G, Chien JY, Fu H, Glass LC, Deeg MA, Holland WL, et al. The effects of LY2405319, an FGF21 analog, in obese human subjects with type 2 diabetes. Cell Metab. 2013;18(3):333-40. [DOI: 10.1016/j.cmet.2013.08.005] [PMID]
[44] Vizvari E, Farzanegi P, Abbas zade H. Effect of Moderate Aerobic Exercise on Serum Levels of FGF21 and Fetuin A in Women with Type 2 Diabete. Medical Laboratory Journa. 2020;14(6):17-22. [DOI: 10.52547/mlj.14.6.17]
[45] Vizvari E, Farzanegi P, Abbas Zade Sourati H. Effect of Vigorous Aerobic Exercise on Serum Levels of SIRT1, FGF21 and Fetuin A in Women with Type II Diabetes. Medical Laboratory Journa. 2018;12(2):1-6. [DOI: 10.29252/mlj.12.2.1]
[46] Abbassi Daloii A, Maleki Delarestaghi A. [The Effect of Aerobic Exercise on Fibroblast Growth Factor 21 and Adiponectin in Obese Men (Persian)]. Journal of Sport Biosciences. 2017;9(1):109-21. [DOI: 10.22059/jsb.2017.61917]
[47] Seydi A and Sheikholeslami-vatani D. [The effects of Resistance Training With High and Moderate Intensities on Lipid ProfileGlycemic Index and FGF21 in Type 2 Diabetic Patients (Persian)]. Journal of Physiology and Management Research in Sports. 2019;11(3):89-103. [Link]
[48] Hajinia M, Haghighi AM and Asgari R. [The effect of intense resistance training on the levels of irisin and fibroblast growth factor 21 in overweight men (Persian)]. Journal of Sabzevar University of Medical Sciences. 2021; 28(3): 457-65. [Link]
[49] Files DC, Sanchez MA, Morris PE. A conceptual framework: the early and late phases of skeletal muscle dysfunction in the acute respiratory distress syndrome. Crit Care. 2015;19(1):266. [DOI: 10.1186/s13054-015-0979-5] [PMID] [PMCID]
[50] Suzuki K, Hekmatikar A.H.A, Jalalian S, Abbasi S, Ahmadi E, Kazemi A, Ruhee R.T, Khoramipour K. The Potential of Exerkines in Women's COVID-19: A New Idea for a Better and
Journal of Medical Sciences
September & October 2024. Vol 22. No 4
Amiri Farsani, et al. Response of Plasma Levels of Selected Myokines to Aerobic and Resistance Exercises in Women Recovered from COVID-19.
JSMJ. 2024; 22(4):526-541
More Accurate Understanding of the Mechanisms behind Physical Exercise. Int J Environ Res Public Health. 2022;19(23):15645. [DOI: 10.3390/ijerph192315645] [PMID] [PMCID]
[51] Chavez AO, Molina-Carrion M, Abdul-Ghani MA, Folli F, DeFronzo RA, Tripathy D. Circulating fibroblast growth factor-21 is elevated in impaired glucose tolerance and type 2 diabetes and correlates with muscle and hepatic insulin resistance. Diabetes Care. 2009;32(8):1542-6. [DOI: 10.2337/ dc09-0684] [PMID] [PMCID]
[52] Soares MN, Eggelbusch M, Naddaf E, Gerrits KHL, Van der Schaaf M, Van den Borst B, Wiersinga WJ, Van Vugt M, Weijs PJM, Murray AJ, Wüst RCI. Skeletal muscle alterations in patients with acute Covid-19 and post-acute sequelae of Covid-19. J Cachexia Sarcopenia Muscle. 2022;13(1):11-22. [DOI: 10.1002/jcsm.12896] [PMID] [PMCID]
[53] McCray PB Jr, Pewe L, Wohlford-Lenane C, Hickey M, Manzel L, Shi L, et al. Lethal infection of K18-hACE2 mice infected with severe acute respiratory syndrome coronavirus. J Virol. 2007;81(2):813-21. [DOI: 10.1128/JVI.02012-06] [PMID] [PMCID]