Acute exercise decreases insulin-stimulated extracellular vesicles in conjunction with augmentation index in adults with obesity

Abstract

Extracellular vesicles (EVs) are often elevated in obesity and may modulate disease risk. Although acute exercise reduces fasting EVs in adults with obesity, no data exist on insulin-mediated EV responses. This study evaluated the effects of exercise on EV responses to insulin in relation to vascular function. Ten (5M/5F) sedentary adults with obesity (34.3 ± 3.7 kg/m² ) completed an evening control and acute exercise condition (70% ${\dot{V}}_{O_2\max }$ to expend 400 kcal). Following an overnight fast, participants underwent a 2 h euglycaemic-hyperinsulinaemic clamp (90 mg/dl; 40 mU/m² /min) to determine metabolic insulin sensitivity (M-value), phenotypes of medium- to large-sized EVs, and aortic waveform measures. Endothelial (CD105⁺ , CD41^- /CD31⁺ )-, leukocyte (CD45⁺ )-, platelet (CD41⁺ , CD41⁺ /31⁺ )- and tetraspanin (TX⁺ )-derived EVs, as well as platelet endothelial cell adhesion molecule (CD31⁺ ), were determined before and after the clamp using high resolution spectral flow cytometry. Although exercise did not alter fasting haemodynamics, it lowered the augmentation index (AIx75, P = 0.024) and increased the M-value (P = 0.042). Further, exercise decreased all fasting EVs (P < 0.01) and decreased insulin-stimulated TX⁺ (P = 0.060), CD31⁺ (P = 0.060) and CD41^- /31⁺ (P = 0.045) compared to rest. Interestingly, greater insulin-stimulated decreases in CD41^- /31⁺ were associated with reduced AIx75 during the clamp (r = 0.62, P = 0.059), while insulin-stimulated decreases in CD41⁺ (r = -0.68, P = 0.031), CD41⁺ /31⁺ (r = -0.69, P = 0.262), TX⁺ (r = -0.66, P = 0.037) and CD31⁺ (r = -0.69, P = 0.028) correlated with M-value following exercise. Thus, acute exercise may decrease fasting and insulin-stimulated medium- to large-size EVs in conjunction with improved M-value and AIx75. More research is needed to understand effects of exercise on EVs in the regulation of glucose homeostasis and vascular function. KEY POINTS: Extracellular vesicles (EVs) are increased in states of obesity and may play a role in altered insulin sensitivity and blood pressure; aerobic exercise decreases fasting EV concentrations the following day in adults with obesity. This study directly tested the effects of insulin on EVs and how a single bout of exercise impacts these responses. Together, these data highlight the positive effects of a single bout of exercise on fasting and insulin-stimulated EVs, with the latter relating to increased insulin sensitivity and decreased augmentation index. These results support future research identifying EVs as mechanistic factors in glucose regulation and vascular function as well as clinical use of exercise to reduce cardiovascular disease risk.

Keywords: aerobic exercise; arterial stiffness; extracellular vesicles; insulin sensitivity.