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

Abstract

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.

What is already known?

What are the new findings?

Muscle-enriched cf-miRNA levels robustly increase following an acute bout of exercise, with temporal and modality specific responses

The implementation of a CHE model, a novel statistical approach within the miRNA field, allowed to identify key methodological factors moderating cf-miRNA levels.

Strict implementation of these factors is warranted to improve rigour and reproducibility in this field.

Competing Interest Statement

The authors have declared no competing interest.

Funding Statement

This study did not receive any funding

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The electronic databases PubMed and SPORTDiscus were searched to identify all relevant articles

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