Multivesicular body and exosome pathway responses to acute exercise

Abstract

New Findings What is the central question of this study?What is the impact of acute aerobic and aerobic + resistance (concurrent) exercise on the regulation of multivesicular body formation in human skeletal muscle? What is the main finding and its importance?Gene expression for proteins associated with multivesicular body biogenesis was increased in response to concurrent exercise, and gene expression of microRNA processing (genetic information) was increased in response to aerobic and concurrent exercise. A greater understanding of the processing of multivesicular bodies in response to acute exercise may lead to novel treatments focused on intercellular communication pathways. Abstract Regular aerobic exercise (AEx) and resistance exercise (REx) promote many beneficial adaptations. Skeletal muscle participates in intercellular communication in part through the release of myokines and extracellular vesicles including exosomes (EXOs), the latter containing mRNA, microRNA (miRNA), lipids and proteins. Exercise‐induced regulation of skeletal muscle multivesicular body (MVB) biogenesis leading to EXO formation and release is poorly understood. We hypothesized that acute exercise would increase skeletal muscle MVB biogenesis and EXO release pathways with a greater response to aerobic + resistance exercise (A+REx) than to AEx alone. Twelve sedentary, healthy male subjects exercised on a cycle ergometer for 45 min (AEx) followed by single leg, knee extensor, resistance exercise (A+REx). Vastus lateralis biopsies were obtained at rest and 1 h post‐exercise. Key components of the MVB biogenesis, EXO biogenesis and release, and miRNA processing pathways were analysed. Clathrin and Alix mRNA (MVB biogenesis) were increased by A+REx, while DICER and exportin mRNA (miRNA processing) were increased by AEx and A+REx. There were positive relationships between MVBs and miRNA processing genes following both AEx and A+REx consistent with coordinated regulation of these interrelated processes (Alix mRNA increased with Drosha, exportin and Dicer mRNA). Acute exercise increases the regulation of components of MVB and EXO pathways as well as miRNA processing components. A greater understanding of the production and packaging of skeletal muscle MVBs, EXOs and mature miRNA could lead to novel treatments focused on intercellular communication.

Extracellular Vesicles and Exosomes: Insights From Exercise Science

“…The observations by Lovett et al (2018) are supported by ELV protein expression studies following a non-damaging, combined exercise intervention (Garner et al, 2020). Participants performed a bout of acute aerobic (45 min of two-legged cycle ergometry at 55% of VO 2max ) or combined exercise (aerobic bout followed by single leg knee extensor exercise at 55% of the 1-RM workload until volitional fatigue), and performing skeletal muscle biopsies from the vastus lateralis of healthy young men (Garner et al, 2020). In comparing pre-to 1 h post-exercise, Garner et al (2020) observed no changes in the protein expression of Alix, TSG101 or CD63 in the vastus lateralis following either exercise protocols.…”

“…Despite evidence of muscle damage (i.e., a ∼5-fold increase in creatine kinase activity from Pre-to 24 h post exercise), there was no evidence of an increase in ELV number or size at either the 2 or 24 h post-exercise timepoints. The observations by Lovett et al (2018) are supported by ELV protein expression studies following a non-damaging, combined exercise intervention (Garner et al, 2020). Participants performed a bout of acute aerobic (45 min of two-legged cycle ergometry at 55% of VO 2max ) or combined exercise (aerobic bout followed by single leg knee extensor exercise at 55% of the 1-RM workload until volitional fatigue), and performing skeletal muscle biopsies from the vastus lateralis of healthy young men (Garner et al, 2020).…”

“…Participants performed a bout of acute aerobic (45 min of two-legged cycle ergometry at 55% of VO 2max ) or combined exercise (aerobic bout followed by single leg knee extensor exercise at 55% of the 1-RM workload until volitional fatigue), and performing skeletal muscle biopsies from the vastus lateralis of healthy young men (Garner et al, 2020). In comparing pre-to 1 h post-exercise, Garner et al (2020) observed no changes in the protein expression of Alix, TSG101 or CD63 in the vastus lateralis following either exercise protocols. Aerobic or combined exercise did not increase the expression of most genes associated with exosome biogenesis or release.…”

Effects of exercise on exosome release and cargo in in vivo and ex vivo models: A systematic review

“…Emerging evidence suggests that exercise enhances the biogenesis of MVBs and exosomes (Garner et al, 2020). Subsequently, the release of exosomes following exercise carries exerkines to mediates intercellular communication (Y.…”

Exosomes as mediators of intercellular crosstalk in metabolism

“…Emerging evidence suggests that exercise enhances the biogenesis of MVBs and the resulting exosomes (Garner et al, 2020). Subsequently, exosome release following exercise can carry exerkines that might modulate intercellular communication (Safdar and Tarnopolsky, 2018).…”