Effects of an acute bout of exercise on circulating extracellular vesicles: tissue-, sex-, and BMI-related differences

Abstract

Background. Exercise is recognized to evoke multisystemic adaptations that, particularly in obese subjects, reduce body weight, improve gluco-metabolic control, counteract sarcopenia and lower the risk of cardiometabolic diseases. Understanding the molecular and cellular mechanisms of exercise-induced benefits is of great interest due to the therapeutic implications against obesity.Objectives and methods. The aim of the present study was to evaluate time-related changes in size distribution and cell origin of extracellular vesicles (EVs) in obese and normal-weight subjects who underwent a moderate-intensity exercise on a treadmill (at 60% of their VO2max). Blood samples were drawn before, immediately at the end of the exercise and during the post-exercise recovery period (3h and 24h). Circulating EVs were analyzed by a nanoparticle tracking analysis and flow cytometry after labeling with the following cellspecific markers: CD14 (monocyte/macrophage), CD61 (platelet), CD62E (activated endothelium), CD105 (total endothelium), SCGA (skeletal muscle) and FABP (adipose tissue).Results. In all subjects, acute exercise reduced the release of total (i.e., 30-700 nm) EVs in circulation, predominantly EVs in the microvesicle size range (i.e., 130-700 nm EVs). The post-exercise release of microvesicles was higher in normal-weight than obese subjects; after exercise, circulating levels of exosomes (i.e., 30-130 nm EVs) and microvesicles were, respectively, lower and higher in females than males. In all experimental subgroups (males vs. females and obese vs. normal-weight subjects), acute exercise reduced and increased, respectively, CD61+ and SCGA+ EVs, being the effect on CD61+ EVs prolonged up to 24h after the end of the test with subjects in resting conditions. Total EVs, exosomes and CD61+ EVs were associated with HOMA-IR.Conclusions. Though preliminary, the results of the present study show that a single bout of acute exercise modulates the release of EVs in circulation, which are tissue-, sex-and BMI specific, suggesting that the exercise-related benefits might depend upon a complex interaction of tissue, endocrine, and metabolic factors.

Considerations for the Analysis of Small Extracellular Vesicles in Physical Exercise

“…Some studies in humans and rodents observed an immediate increase of sEVs after a single bout of physical exercise (Frühbeis et al, 2015;Bei et al, 2017;Oliveira et al, 2018;Whitham et al, 2018;Brahmer et al, 2019). One study found a direct reduction of total EV numbers, while detecting an increased population of muscle cell-derived EVs (Rigamonti et al, 2019). Furthermore, elevation of resting EV levels were detected in response to long-term exercise interventions (Chaturvedi et al, 2015;Bei et al, 2017;Bertoldi et al, 2018;Ma et al, 2018), though Hou et al (2019) could not detect changes in EV levels.…”

“…Furthermore, elevation of resting EV levels were detected in response to long-term exercise interventions (Chaturvedi et al, 2015;Bei et al, 2017;Bertoldi et al, 2018;Ma et al, 2018), though Hou et al (2019) could not detect changes in EV levels. ExerVs appear as a complex mixture of vesicles originating from platelets (Frühbeis et al, 2015;Brahmer et al, 2019), endothelial progenitor, or endothelial cells (Ma et al, 2018;Brahmer et al, 2019;Hou et al, 2019), leukocytes (Brahmer et al, 2019), and muscle cells (Guescini et al, 2015;Whitham et al, 2018;Rigamonti et al, 2019), which most probably varies depending on exercise mode and time of investigation.…”

“…Interestingly, no major discrepancies in the characteristics of ExerVs were detected between human, mouse, or rat models. Though, several aspects were identified which may influence specific results, including exercise setting (e.g., load or type of exercise; Frühbeis et al, 2015;Ma et al, 2018;Whitham et al, 2018;Brahmer et al, 2019;Yin et al, 2019), daytime (Bertoldi et al, 2018), age (Bertoldi et al, 2018), sex (Rigamonti et al, 2019), and body-mass-index (Rigamonti et al, 2019).…”

“…The present reports on sEVs or exosome-like EVs in exercise settings comprise a collection of multiple different EV isolation methods and characterization strategies. Diverse separation methods were used to study the amount, cargo and functions of ExerVs from human, mouse, and rat plasma or serum: centrifugation at 20,000 × g (Whitham et al, 2018), dUC (Chaturvedi et al, 2015;Frühbeis et al, 2015;Guescini et al, 2015;Ma et al, 2018;Hou et al, 2019;Rigamonti et al, 2019), chemical precipitation (Bei et al, 2017;Bertoldi et al, 2018;Oliveira et al, 2018;Hou et al, 2019;Yin et al, 2019;Just et al, 2020), SEC (D'souza et al, 2018;Lovett et al, 2018;Brahmer et al, 2019;Just et al, 2020), immuno-affinity capture (Guescini et al, 2015;Ma et al, 2018;Brahmer et al, 2019), and acoustic trapping (Bryl-Górecka et al, 2018). Importantly, these studies consistently reported increasing amounts of EVs during or after acute or chronic exercise, changes in the miRNA and proteomic cargo of ExerVs as well as beneficial effects of ExerVs in key signaling pathways.…”

Extracellular vesicles as predictors of individual response to exercise training in youth living with obesity

“…Another study showed that acute AE was associated with an increase in EV concentration and the presence of twelve different miRNA in their cargo (46). In contrast, in obese adults, Rigamonti et al (2019) reported reduced EVs concentration immediately at the end of AE and after 3h and 24 h (47). No studies have been conducted on EV release with AE in youth with obesity to our knowledge.…”