The miRNA Plasma Signature in Response to Acute Aerobic Exercise and Endurance Training

Søren Nielsen,Bente K Pedersen,Christina Yfanti,Matthew J Laye,Thorbjörn Åkerström,Anders Rinnov,Camilla Scheele,Juergen Eckel

doi:10.1371/journal.pone.0087308

Søren Nielsen, Bente K Pedersen + Show 6 more

Open Access

https://doi.org/10.1371/journal.pone.0087308

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Abstract

MiRNAs are potent intracellular posttranscriptional regulators and are also selectively secreted into the circulation in a cell-specific fashion. Global changes in miRNA expression in skeletal muscle in response to endurance exercise training have been reported. Therefore, our aim was to establish the miRNA signature in human plasma in response to acute exercise and chronic endurance training by utilizing a novel methodological approach. RNA was isolated from human plasma collected from young healthy men before and after an acute endurance exercise bout and following 12 weeks of endurance training. Global miRNA (742 miRNAs) measurements were performed as a screening to identify detectable miRNAs in plasma. Using customized qPCR panels we quantified the expression levels of miRNAs detected in the screening procedure (188 miRNAs). We demonstrate a dynamic regulation of circulating miRNA (ci-miRNA) levels following 0 hour (miR-106a, miR-221, miR-30b, miR-151-5p, let-7i, miR-146, miR-652 and miR-151-3p), 1 hour (miR-338-3p, miR-330-3p, miR-223, miR-139-5p and miR-143) and 3 hours (miR-1) after an acute exercise bout (P<0.00032). Where ci-miRNAs were all downregulated immediately after an acute exercise bout (0 hour) the 1 and 3 hour post exercise timepoints were followed by upregulations. In response to chronic training, we identified seven ci-miRNAs with decreased levels in plasma (miR-342-3p, let-7d, miR-766, miR-25, miR-148a, miR-185 and miR-21) and two miRNAs that were present at higher levels after the training period (miR-103 and miR-107) (P<0.00032). In conclusion, acute exercise and chronic endurance training, likely through specific mechanisms unique to each stimulus, robustly modify the miRNA signature of human plasma.

Highlights

MiRNAs are 20-24 nucleotides non-coding RNAs that regulate protein abundance primarily by binding to the 39UTR of coding mRNAs [1]
A single miRNA can regulate the expression of hundreds of mRNAs and proteins [2,3] and are significant player in regulating many aspects of biology [4,5,6]
We noted that the expression levels of spike-in RNA added during the RNA isolation and cDNA synthesis step did not vary between samples when quantifying with quantitative real-time PCR (qPCR), suggesting equivalent RNA isolation and cDNA synthesis

Summary

Introduction

MiRNAs are 20-24 nucleotides non-coding RNAs that regulate protein abundance primarily by binding to the 39UTR of coding mRNAs [1]. Aerobic and resistance exercise interventions alter the global transcriptional miRNA pattern of these tissues [10,11,12,13]. These changes in miRNA expression provide numerous novel explanations for the effects of training on metabolism. An acute aerobic exercise intervention down regulates miR-23a expression in skeletal muscle in both humans and mice [12,14]. The exercise induced alteration in miRNA expression is a likely muscular adaptation mechanism in response to endurance training

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