Circulating and skeletal muscle microRNA profiles are more sensitive to sustained aerobic exercise than energy balance in males

Abstract

MicroRNAs (miRNAs) regulate molecular processes governing muscle metabolism. Physical activity and energy balance influence both muscle anabolism and substrate metabolism, but whether circulating and skeletal muscle miRNAs mediate those effects remains unknown. This study assessed the impact of sustained physical activity with participants in energy balance (BAL) or deficit (DEF) on circulating and skeletal muscle miRNAs. Using a randomized cross‐over design, 10 recreational active healthy males (mean ± SD, 22 ± 5 years, 87 ± 11 kg) completed 72 h of high aerobic exercise‐induced energy expenditures in BAL (689 ± 852 kcal/day) or DEF (−2047 ± 920 kcal/day). Blood and muscle samples were collected under rested/fasted conditions before (PRE) and immediately after 120 min load carriage exercise bout at the end (POST) of the 72 h. Trials were separated by 7 days. Circulating and skeletal muscle miRNAs were measured using microarray RT‐qPCR. Independent of energy status, 36 circulating miRNAs decreased (P < 0.05), while 10 miRNAs increased and three miRNAs decreased in skeletal muscle (P < 0.05) at POST compared to PRE. Of these, miR‐122‐5p, miR‐221‐3p, miR‐222‐3p and miR‐24‐3p decreased in circulation and increased in skeletal muscle. Two circulating (miR‐145‐5p and miR‐193a‐5p) and four skeletal muscle (miR‐21‐5p, miR‐372‐3p, miR‐34a‐5p and miR‐9‐5p) miRNAs had time‐by‐treatment effects (P < 0.05). These data suggest that changes in miRNA profiles are more sensitive to increased physical activity compared to energy status, and that changes in circulating miRNAs in response to high levels of daily aerobic exercise are not reflective of changes in skeletal muscle miRNAs. Key points Circulating and skeletal muscle miRNA profiles are more sensitive to high levels of aerobic exercise‐induced energy expenditure compared to energy status. Changes in circulating miRNA in response to high levels of daily sustained aerobic exercise are not reflective of changes in skeletal muscle miRNA.

Micro(RNA)‐cloud can perpetuate physiological adaptation of skeletal muscle to exercise and energy imbalance

“…Circulating microRNAs are considered non-invasive biomarkers of such adaptive changes in muscle and other tissues, because their levels are often responsive to various physiological stimuli. Consistent with the work of other research groups (D'Souza et al, 2018), Margolis et al (2022) demonstrated downregulation of many circulating microRNAs, in addition to changes in microRNA levels in skeletal muscle, suggesting a circulating micro-RNA blueprint characterizing changes in response to exercise and less so in response to energy deficiency. Although circulating microRNAs are often considered by-products of cell activity, such as cell death, it is likely that the release of micro-RNAs is a regulated process, and micro-RNAs can act as messengers between cells and tissues, contributing to adaptation at the level of multiple tissues.…”

“…Sannicandro et al, 2020). Margolis et al (2022) demonstrated that among microRNAs upregulated in skeletal muscle mainly after exercise, with a few microRNAs responsive to energy imbalance, were microRNAs associated with processes known to be involved in muscle adaptation to exercise. In addition, the authors performed analysis of mRNA levels of predicted targets of altered microRNAs.…”

“…In this issue of The Journal of Physiology , Margolis et al. (2022) have demonstrated that the levels of circulating and skeletal muscle microRNAs change in response to high levels of aerobic exercise, in addition to energy deficiency. Previously, microRNAs have been reported to respond to energy deficiency, e.g.…”

The independency of miRNA to energy status

“…Prior to the exercise, baseline blood and muscle samples from a biopsy of vastus lateralis were collected following a 10 h overnight fast and labelled as PRE (Margolis et al. 2022). Immediately post‐exercise, another blood sample was taken, and a muscle biopsy was performed, and labelled as POST.…”

“…Prior to the 72 h of exercise, each participant had their glycogen levels standardized in 48 h (Margolis et al. 2022).…”