Effects of Different Training Modalities on Circulating Irisin Levels in Overweight and Obesity Adults: A Systematic...

Irisin is an exercise-induced myokine that has been proposed to exert beneficial effects on metabolic health. However, its response to different exercise training modalities in individuals with overweight or obesity remains inconsistent. This systematic review and meta-analysis primarily aimed to evaluate the effects of various exercise interventions on circulating irisin levels as the primary outcome in overweight and obese adults. Additionally, we assessed changes in other selected myokines and metabolic markers as secondary outcomes to provide a better understanding of exercise induced physiological adaptations.

A systematic search was conducted in Web of Science, EMBASE, Cochrane Library, PubMed, SCOPUS, and Google Scholar (up to 22 April 2025) to identify randomized controlled trials (RCTs) evaluating the effects of different exercise training protocols (aerobic, resistance, concurrent, and high-intensity interval training) on circulating irisin levels in adults with overweight or obesity. The primary eligibility criterion to include studies was the measurement of circulating irisin. Within the RCTs meeting this criterion, we additionally extracted data on selected myokines (follistatin, myostatin, and FGF21) and metabolic markers (glycemic control and lipid profiles) when reported. These secondary outcomes were analyzed to contextualize irisin responses within broader metabolic adaptations, but no separate systematic search was performed for these variables. Pooled effect sizes were calculated using random-effects models and expressed as standardized mean differences (SMDs) with 95% confidence intervals (CIs). Using the median split technique, subgroup analyses were computed according to exercise training modality.

A total of 50 studies comprising 1780 participants (1104 in exercise groups and 676 in passive control groups) were included. For the primary outcome, exercise training was associated with a significant increase in circulating irisin (SMD 0.62, 95% CI 0.39-0.85, p < 0.001, n = 76 arms, 1721 subjects) compared with passive controls. Among the secondary outcomes, training was also associated with increases in high-density lipoprotein cholesterol (SMD 0.25, 95% CI 0.03-0.47, p = 0.030], n = 18 arms, 420 subjects), follistatin (SMD 0.89, 95% CI 0.37-1.41, p = 0.008, n = 7 arms, 141 subjects), and fibroblast growth factor 21 (FGF-21; SMD 1.00, 95% CI 0.10-1.91, p = 0.003, n = 13 arms, 280 subjects). In contrast, exercise training did not significantly affect myostatin levels (SMD - 0.45, 95% CI - 1.07 to 0.18, p = 0.160, n = 11 arms, 283 subjects). Additionally, exercise training significantly reduced fasting blood glucose (SMD - 0.61, 95% CI - 0.89 to - 0.33, p < 0.001, n = 28 arms, 696 subjects), insulin (SMD - 0.80, 95% CI - 1.11 to - 0.50, p < 0.001, n = 24 arms, 566 subjects), homeostatic model assessment for insulin resistance (SMD - 0.75, 95% CI - 1.08 to - 0.43, p < 0.001, n = 28 arms, 609 subjects), hemoglobin A1C (HbA1C) (SMD - 0.96, 95% CI - 1.23 to - 0.70, p < 0.001, n = 12 arms, 275 subjects), and low-density lipoprotein cholesterol (SMD - 0.38, 95% CI - 0.74 to - 0.02, p = 0.040, n = 18 arms, 443 subjects). Exploratory subgroup analysis showed significant increases in irisin following resistance training (SMD 0.88 [95% CI, 0.44 to 1.33], [p = 0.001], n = 21 arms, 537 subjects, I² = 79% [p = 0.001]), high-intensity interval training (SMD 0.61 [95% CI, 0.13 to 1.09], [p = 0.001], n = 17 arms, 346 subjects, I² = 75% [p = 0.001]), and concurrent training (SMD 0.42 [95% CI, 0.16 to 0.68], [p = 0.002], n = 18 arms, 356 subjects, I² = 21% [p = 0.20]). Although resistance training demonstrated numerically larger effects, differences between exercise modalities were not statistically significant (p > 0.05).

Regular exercise is an effective intervention for increasing circulating irisin levels and favorably modulating other myokines such as follistatin and FGF-21 in adults with overweight or obesity. Resistance training showed larger numerical effects, but the differences between exercise types were not statistically significant. These adaptations, alongside improvements in metabolic markers, support the role of structured exercise as part of a comprehensive strategy for improving metabolic health in this population.

PROSPERO CRD42025637476.