Impact of Exercise Training and Feeding on Circulating Extracellular Vesicles in Adults with Obesity

First described by Wolf in 1967 as only “cell dust”, extracellular vesicles (EVs) have emerged as novel biomarkers and/or mediators of chronic diseases such as cardiovascular disease (CVD) and type 2 diabetes (T2D). As both exercise and diet interventions are known to reduce CVD and T2D risk, it is clinically relevant to determine the impact of such interventions in relation to EV count and subtype. Despite this relevance, most previous work in the field lack sensitivity to optimally enrich and phenotype EVs, as the current approach of frozen samples and conventional flow cytometry may impact the clarity and precision of results. Therefore, the combination of fresh blood samples and imaging flow cytometry to characterize EVs in relation to feeding and exercise interventions is crucial for understanding the roles EVs may play in cardiometabolic disease risk and progression. The focus of Aim 1 was to characterize EVs utilizing fresh blood samples and imaging flow cytometry in relation to cardiorespiratory fitness, a strong independent predictor of all-cause mortality and CVD. We found that in adults with obesity, those with lower levels of fitness (15.4±0.6 ml/kg/min) had higher levels of total, Annexin V- (AV) platelet (CD31+/CD41+) and endothelial-derived (CD31+/CD41-) EVs than those with higher levels of fitness (25.9±3.0 ml/kg/min), independent of age or body fat. Aim 2 was to determine the impact of high-glucose feeding on EV count in adults with both normal glucose tolerance (NGT) and prediabetes (PD). We found that regardless of glucose status, total, AV+ endothelial (CD31+/CD41+) and AV+ CD31+ platelet endothelial cell adhesion molecule 1(PECAM-1) EVs were significantly lowered following a 75 g oral glucose challenge, whereas postprandial elevations in total EVs were also related to decreased arterial stiffness and increased insulin resistance. In Aim 3, the impact of short-term exercise intensity on circulating EVs in adults with prediabetes was determined. We found that while 12 days of training had no effect on platelet or leukocyte EVs, interval exercise significantly decreased the endothelial EV AV- CD105 compared with continuous training. Those individuals who had the greatest improvements in cardiorespiratory fitness saw the greatest decreases in AV- CD105, supporting our findings in Aim 1 that EV count may in part be modulated by differences in fitness. When accounting for changes in dietary sugar consumption, however, the intensity effect was no longer significant, supporting our results presented in Aim 2 that showed EVs might also be modulated by high glucose conditions. Taken together, our findings from this work suggests that both dietary and exercise interventions modulate EV count in conjunction with changes in clinical outcomes such as cardiorespiratory fitness, arterial stiffness and insulin resistance.