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

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


Extended Abstract
Introduction ecently, performing regular sports activities has been considered an effective strategy for the rehabilitation of patients who have recovered from COVID-19.COVID-19 is a global pandemic with clinical manifestations varying from an asymptomatic or mild illness to severe viral pneumonia that may lead to acute respiratory distress [1].Numerous people with COVID-19 in the world are recovering while facing various complications [3].This virus disrupts the reninangiotensin system, increases myostatin and interleukin 6 (IL-6) levels, and decreases insulin-like growth factor 1 (IGF-1).Moreover, it is responsible for the breakdown and reduction of protein synthesis.In addition, the occurrence of cytokine storm, immobility, and consumption of corticosteroids will accelerate muscle proteolysis [4].With the reduction of muscle mass in COVID-19 patients, the balance in the myokine profile is disturbed, and their protective role on other organs is reduced.Consequently, muscle loss and its subsequent complications should be taken into consideration in these patients [6].Physical activity and exercise are recognized as a healthy gold standard and an effective non-pharmacological approach to several chronic diseases [8].Sports activities can improve their performance by increasing the number of myokines and prevent the occurrence of COVID-19-related diseases through cross-talk between skeletal muscles and other organs.It also helps people to return to normal life faster [6].Irisin is a member of the myokine family that is secreted from skeletal muscle cells by breaking the fibronectin type III domain containing 5 (FNDC5) protein [11].Based on these studies, increasing the levels of myokines secreted from muscle, including irisin, can reduce oxidative stress and improve lung function in COVID-19 patients [6].Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) increases muscle proteolysis by disrupting myokine homeostasis (boosting myostatin levels and decreasing IGF-1 levels) [4].As demonstrated by studies, performing sports activities in COVID-19 patients can effectively reduce cytokine storm and its complications by increasing the expression of proteins, such as follistatin [2].The possibility of long-term metabolic complications caused by COVID-19 should also be considered [17].The use of compounds derived from myokines or the provision of specific exercise regimens can be promising in the treatment of metabolic diseases [19].Considering the presence of myokine homeostasis disorders in these patients, the question arises whether doing aerobic and resistance exercises will change the plasma levels of myokines.In light of the aforementioned issues, the present study aimed to assess the effect of eight-week selected aerobic and resistance training on the plasma levels of irisin, follistatin, and FGF21 in women recovered from COVID-19.

Methods
The current research was conducted based on a quasi-experimental design.A total of 33 women who recovered from COVID-19 were selected using convenience and purposeful sampling methods and were assigned to three groups, namely aerobic training, resistance training, and control (n=11 in each group).Blood samples were taken from all subjects 48 h before the initiation of the training protocol and 48 h after the last training session.The protocol of aerobic exercises with an intensity of 50%-70% of the reserve heart rate and the protocol of resistance exercises with an intensity of 40%-75% of a maximum repetition were implemented for eight weeks (three sessions per week).Shapiro-Wilk test was used to check the normality of data distribution.Levene's test was utilized to check the homogeneity of variances; moreover, descriptive statistics were utilized to calculate central and dispersion indices.After ensuring the normality of the data, one-way analysis of variance and paired t-test were used to compare the average parameters at the P ≤ 0.05 level.

Results
Examining the statistical results of the difference of means illustrated a significant difference between irisin response to exercise among the groups (P<0.05).Bonferroni post hoc test demonstrated that the difference between aerobic and control groups (P<0.05), as well as resistance and control groups (P<0.05), was significant; nonetheless, the aerobic and resistance groups displayed no significant difference.The statistical analysis of the mean difference in follistatin plasma levels showed a significant difference between the response of follistatin to exercise among the groups (P<0.05).Banferoni's post hoc test exhibited significant changes between aerobic and control groups, as well as resistance and control groups.Examining the results of serum levels of FGF21 pointed to a significant difference in the response to exercise among the groups (P<0.05).Banferoni's post hoc test suggested significant changes between aerobic and control groups as well as resistance and control groups (P<0.05).Nevertheless, there was no significant difference between aerobic and resistance groups.

Conclusion
As evidenced by the obtained results, performing eight weeks of selected aerobic and resistance exercises led to a significant increase in the amounts of irisin, follistatin, and FGF21 in both experimental groups.In humans, FNDC5 mRNA is mainly expressed in skeletal muscle and other muscle-containing organs.The main predictor of the highest circulating irisin level is muscle mass.Meanwhile, PGC-1α has a major role to play in the regulation of irisin secretion.The activation of adenosine monophosphate-activated protein kinase leads to the activation of PGC-1α as a regulator of FNDC5 expression and will increase the secretion of irisin.Furthermore, according to studies, regular physical activities can reduce acute inflammation caused by SARS-CoV-2 infection by reducing the activity of the R inflammatory signaling pathway of Toll-like receptors, increasing the levels of anti-inflammatory cytokines IL-10 and IL-37 [28].Therefore, it can be concluded that the improvement of the inflammatory conditions of the body in these patients can be among the other reasons for increasing the expression of useful myokines secreted from the muscle, including irisin.
The mechanism of follistatin secretion is not fully understood.Based on the studies, sports exercises can be effective in improving people's physical condition by creating a balance between the positive and negative regulators of muscle growth.Muscle contraction, stretching of muscle contractile proteins, and mechanical load can be effective in the release of myogenic factors, including follistatin [34].Training duration is another factor that regulates muscle growth factor, especially follistatin; thus, aerobic exercises also enhance the structure of muscle tissue by boosting follistatin levels [33].
According to human studies, one of the determinants of plasma FGF21 concentration is the muscle mass of the whole body [47].Since resistance exercises are associated with an increase in the hypertrophy capacity of skeletal muscles, it can be argued that the increase in FGF21 levels in the resistance group can be ascribed to muscle mass recovery.Moreover, elevated values of FGF21 in the aerobic group can be attributed to the improvement of the structure and metabolic behavior of the muscle tissue, as well as the reduction of inflammation due to the selection of the appropriate intensity and duration of the training protocol.