Response of circulating miRNAs to acute exercise: A systematic Review and Meta-Analysis

Objective: Cell-free microRNAs (cf-miRNAs) are secreted from cells and transported via the blood to exert their effect on target tissues. Numerous pathophysiological adaptations, including exercise, alter cf-miRNA levels. The aim of the systematic review was to investigate the cf-miRNA response to an acute bout of exercise and to interpret it using a robust correlated and hierarchical effects (CHE) meta-analysis. Design: The systematic review was registered in PROSPERO (CRD42021256303). A CHE meta-analysis was used to compare the changes in cf-miRNA levels and the influence of exercise modality. An exploratory machine-learning-based approach was used to capture influential moderators. Data sources: Primary studies were retrieved from PubMed and SPORTDiscus (09.03.2022). Relative changes in cf-miRNA expression in response to exercise were computed for each study. The ROBINS-I, GRADE and AMSTAR2 tools were used to assess evidence certainty and risk of bias. Eligibility criteria: Thirty-six studies including an acute exercise intervention in N=880 healthy males and females aged 18-45yrs met the eligibility criteria. Results: Muscle enriched cf-miR-1 (N=320), cf-miR-133a (N=195) and cf-miR-133b (N=132) levels increased 1-2hr (cf-miR1: FC = 2.72, 95% CI= 1.5-4.0; cf-miR133a: FC = 2.10, 95% CI = 1.6-2.6; cf-miR-133b: FC = 2.39, 95% CI = 1.2-3.6) and 24 hr post-exercise (cf-miR1: FC = 2.25, 95% CI= 1.3-3.2; cf-miR133a: FC = 1.81, 95% CI = 1.4-2.2; cf-miR-133b: FC = 1.99, 95% CI = 1.2-2.8). Conclusion: Acute exercise triggers temporal and modality specific responses in cf-miRNAs. levels. Influential moderators included sample size, collection time point, exercise modality, age and the use of various technical quality controls.