Low cardiorespiratory fitness is associated with higher extracellular vesicle counts in obese adults

Low cardiorespiratory fitness (CRF) is associated with cardiovascular disease (CVD) independent of obesity. Extracellular vesicles (EVs) are a novel target of CVD, however, it remains unknown if obese individuals with very poor fitness (VPF) have elevated EVs versus people with poor fitness (PF). Thus, we tested whether VPF was associated with greater EV subtypes in obese adults. Subjects with VPF (n = 13, VO₂ peak: 15.4 ± 0.6 mL/kg/min, BMI: 34.1 ± 1.7 kg/m² ) and PF (n = 13, VO₂ peak: 25.9 ± 3.0 mL/kg/min, BMI: 32.1 ± 1.2 kg/m² ) were compared in this cross-sectional study. After an overnight fast, AnnexinV (AV) +/- platelet (CD31⁺ /CD41⁺ ), leukocyte (CD45⁺ /CD41^- ), and endothelial EVs (CD105⁺ , CD31⁺ /CD41^- ) were analyzed from fresh platelet poor plasma via imaging flow cytometry. Body fat, blood pressure (BP), and glucose tolerance (OGTT) were also tested. Body weight, BP, and circulating glucose were similar between groups, although VPF subjects were older than PF (64.0 ± 2.1 vs. 49.8 ± 4.2 year; P < 0.05). People with VPF, compared with PF, had higher total AV^- EVs (P = 0.04), AV^- platelet EVs (CD31⁺ /CD41⁺ ; P = 0.006), and AV^- endothelial EVs (CD31⁺ /CD41^- ; P = 0.005) independent of age and body fat. Higher AV^- platelet and endothelial EVs were associated with lower VO₂ peak (r = -0.56, P = 0.006 and r = -0.55, P = 0.005, respectively). Endothelial-derived AV^- /CD31⁺ /CD41^- EVs were also related to pulse pressure (r = 0.45, P = 0.03), whereas AV^- /CD105 was linked to postprandial glucose (r = 0.41, P = 0.04). VPF is associated with higher AnnexinV^- total, endothelial, and platelet EVs in obese adults, suggesting that subtle differences in fitness may reduce type 2 diabetes and CVD risk through an EV-related mechanism.