Specific circulating microRNAs display dose-dependent responses to variable intensity and duration of endurance exercise

Abstract

Circulating microRNAs (c-miRNAs), plasma-based noncoding RNAs that control posttranscriptional gene expression, mediate processes that underlie phenotypical plasticity to exercise. The relationship and biological relevance between c-miRNA expression and variable dose exercise exposure remains uncertain. We hypothesized that certain c-miRNAs respond to changes in exercise intensity and/or duration in a dose-dependent fashion. Muscle release of such c-miRNAs may then deplete intracellular stores, thus facilitating gene reprogramming and exercise adaptation. To address these hypotheses, healthy men participated in variable intensity ( n = 12, 30 × 1 min at 6, 7, and 8 miles/h, order randomized) and variable duration ( n = 14, 7 × 1 mile/h for 30, 60, and 90 min, order randomized) treadmill-running protocols. Muscle-enriched c-miRNAs (i.e., miRNA-1 and miRNA-133a) and others with known relevance to exercise were measured before and after exercise. c-miRNA responses followed three profiles: 1) nonresponsive (miRNA-21 and miRNA-210), 2) responsive to exercise at some threshold but without dose dependence (miRNA-24 and miRNA-146a), and 3) responsive to exercise with dose dependence to increasing intensity (miRNA-1) or duration (miRNA-133a and miRNA-222). We also studied aerobic exercise-trained mice, comparing control, low-intensity (0.5 km/h), or high-intensity (1 km/h) treadmill-running protocols over 4 wk. In high- but not low-intensity-trained mice, we found increased plasma c-miR-133a along with decreased intracellular miRNA-133a and increased serum response factor, a known miR-133a target gene, in muscle. Characterization of c-miRNAs that are dose responsive to exercise in humans and mice supports the notion that they directly mediate physiological adaptation to exercise, potentially through depletion of intracellular stores of muscle-specific miRNAs. NEW & NOTEWORTHY In this study of humans and mice, we define circulating microRNAs in plasma that are dose responsive to exercise. Our data support the notion that these microRNAs mediate physiological adaptation to exercise potentially through depletion of intracellular stores of muscle-specific microRNAs and releasing their inhibitory effects on target gene expression.

MicroRNAs as Biomarkers of Systemic Changes in Response to Endurance Exercise—A Comprehensive Review

“…Several studies evaluated the involvement of a number of miRNAs in cardiac hypertrophy, however, the results are conflicting [ 11 , 16 , 17 , 18 ]. Moreen et al investigated a relation of miRNAs with conventional biochemical, cardiovascular, and performance indices in endurance athletes before, immediately after, and 24 h after a marathon run.…”

Changes in circulating microRNA and arterial stiffness following high‐intensity interval and moderate intensity continuous exercise

“…recently identified ci‐miRs with either threshold or dose‐response kinetics to exercise by having men run at variable speeds or durations, while holding the other variable constant ( Ramos et al., 2018). The only ci‐miR also tested in our study, ci‐miR‐21‐5p, failed to increase and, therefore, did not show an intensity‐dependent response in their study ( Ramos et al., 2018). Conversely, we observed no change in ci‐miR‐21‐5p in response to a MOD exercise bout, but a ~ two‐fold increase in response to a HII exercise bout.…”

Circulating microRNAs in Response to Exercise Training in Healthy Adults

“…The changes of circulating miRNAs induced by exercise have been widely reported in healthy persons and patients, indicating miRNAs may play a role in physiological adaptations to exercise. Profiles of circulating miRNAs are varying under different exercise type, duration and intensity (Xu et al, 2016;de Gonzalo-Calvo et al, 2018;Horak et al, 2018;Li et al, 2018;Ramos et al, 2018;Sapp and Hagberg, 2019). However, less is known about the changes of circulating miRNAs in the adaptation to cardiopulmonary exercise testing (CPET) and acute exercise training (AET).…”