Dynamic transcriptomic responses to divergent acute exercise stimuli in young adults

Abstract

Acute exercise elicits dynamic transcriptional changes that, when repeated, form the fundamental basis of health, resilience, and performance adaptations. While moderate-intensity endurance training combined with conventional resistance training (traditional, TRAD) is often prescribed and recommended by public health guidance, high-intensity training combining maximal-effort intervals with intensive, limited-rest resistance training is a time-efficient alternative that may be used tactically (HITT) to confer similar benefits. Mechanisms of action of these distinct stimuli are incompletely characterized and have not been directly compared. We assessed transcriptome-wide responses in skeletal muscle and circulating extracellular vehicles (EVs) to a single exercise bout in young adults randomized to TRAD (n=21, 12M/9F, 22±3y) or HITT (n=19, 11M/8F, 22±2y). Next-generation sequencing captured small, long, and circular RNA in muscle and EVs. Analysis identified differentially expressed transcripts (|log2FC|>1, FDR≤0.05) immediately (h0, EVs only), h3, and h24 post-exercise within and between exercise protocols. Additionally, all apparently responsive transcripts (FDR<0.2) underwent singular value decomposition to summarize data structures into latent variables (LVs) to deconvolve molecular expression circuits and inter-regulatory relationships. LVs were compared across time and exercise protocol. TRAD, a longer but more sustained stimulus, generally elicited a stronger transcriptional response than HITT, but considerable overlap and key differences existed. Findings reveal shared and unique molecular responses to the exercise stimuli and lay groundwork toward establishing relationships between protein-coding genes and lesser-understood transcripts that serve regulatory roles following exercise. Future work should advance the understanding of these circuits and whether they repeat in other populations or following other types of exercise/stress.

MicroRNA‐92b in the skeletal muscle regulates exercise capacity via modulation of glucose metabolism

“…Through reanalysis of the database obtained from GSE209880, 35 we found that both miR‐92b‐3p and miR‐92b‐5p expression in the skeletal muscle were increased after 24 h of a single exercise bout, as compared with baseline (Figure S7E ). Consistently, we found that a single exercise bout upregulated the expression of both miR‐92b‐3p and miR‐92b‐5p in the skeletal muscle of mice (Figure S7D ).…”

Combined aerobic and resistance exercise training alters the spatial transcriptome of skeletal muscle in young adults

“…Biospecimens used in this study were obtained from a parent clinical trial comparing traditional combined exercise versus high-intensity combined exercise prescriptions (Department of Defense, Office of Naval Research: N000141613159, ClinicalTrials.gov ID: NCT0330923). We have previously described the recruitment, eligibility, screening and randomization strategies for these participants 7 . In brief, males and females aged 18-27 were recruited from the greater Birmingham, AL area.…”

“…Skeletal muscle is a complex tissue containing, in addition to primary myofibers, numerous non-myofiber cell types and associated structures (e.g., neural, vascular, connective, and adipose tissues along with immune cells, stem cells, etc.). Traditional approaches to muscle transcriptomics have mostly relied on bulk sequencing of RNA isolated from whole tissue [6][7][8][9] or from single cell/nuclei isolated from the muscle environment [10][11][12] . While these data have been invaluable, they are incomplete as they lack important architectural information about the local cellular environment and origin of the RNA as the tissue adapts to exercise training.…”