Effect of a 12-Week Endurance Training Program on Circulating Extracellular Vesicle Proteome in Sedentary Adults With Obesity

Abstract

Systemic inflammatory state found in obesity increases the risk of developing numerous diseases. While endurance training seems effective to reduce this inflammation, the underlying mechanisms are not fully understood. Among those, extracellular vesicles (EVs) have been proposed to be actors in the anti-inflammatory intercellular crosstalk induced by exercise training. This study aimed to investigate how endurance training modulates the EV proteome in the context of an inflammatory state in adults with obesity. Thirteen lean sedentary adults and 10 sedentary adults with obesity participated in a 12-week endurance training programme. Skeletal muscle, abdominal subcutaneous adipose tissue and venous blood samples were taken prior to and after the training period. The systemic and adipose tissue inflammatory states were assessed, and plasma EVs were isolated by size exclusion chromatography. EV content was analysed by mass spectrometry. EVs isolated from the medium of myotubes stimulated by electrical pulse stimulation in vitro were quantified, and their content was analysed by western blot. After the endurance training, C-reactive protein (CRP) levels decreased in participants with obesity. In abdominal subcutaneous adipose tissue, the phosphorylation state of nuclear factor-kappa B (NF-kappa B) was not affected by training, but interleukin (IL)-6 and IL-1 beta protein levels were reduced after the 12 weeks in both groups. Conversely, interferon gamma (IFN gamma) level reduction was exclusively found in the obesity group. Despite no changes in EV abundance, EV proteome was modified by training. Among the modified proteins in participants with obesity, the antioxidant enzyme peroxiredoxin (PRDX) 1 abundance was increased after training. Additionally, the PRDX1 content of EVs isolated from stimulated myotubes was increased compared to control conditions. In conclusion, our results suggest that the anti-inflammatory effects of exercise training are not directly mediated by EV anti-inflammatory proteome changes. However, exercise training increases circulating EV antioxidant content, possibly through contractile activity of skeletal muscle during repeated exercise.