Endocrine Abstracts

Introduction: Extracellular vesicles (EVs) are submicron vesicles released by most cells. They contain protein, enzymes and microRNA of the donor cells and are believed to play a role in paracrine communication. Circulating EVs might reflect heightened immune/inflammatory status in obese individuals and play a role in initiation/modulation of chronic low grade inflammation associated with obesity.

Aims: To compare circulating plasma EVs between healthy volunteers and morbidly obese individuals attending a multidisciplinary weight loss clinic, and to assess the effects of lifestyle changes on the circulating EV profile.

Methods: EVs were isolated by differential centrifugation and measured by Nanoparticle Tracking Analysis (NTA). EV cellular origin (platelets CD41, monocytes/macrophages CD11b, erythrocytes CD235a, endothelial cells CD144) and adipocytokine expression (IL6, TNFα, interferon γ, adiponectin, FABP4, PPARγ) were evaluated by TRF immunoassay.

Results: Circulating EV profile and concentration in metabolically healthy volunteers was unaffected by BMI (all P=ns). However, the EV profile in healthy men appears to be more pro-inflammatory compared to women, with higher EV-expressed CD41, CD144, EV-IL6, interferon γ and FABP4 (all P<0.05). This was also reflected by lower plasma adiponectin concentration in males (128 μg/ml vs 272.3 μg/ml, P<0.005). Plasma FABP4 correlated strongly with BMI (r=0.91, P<0.005) and was lower in healthy lean versus obese individuals (13.5(6.4) vs 23.8(6.4) ng/ml, respectively (P<0.05)) despite fasting glucose and HOMA-IR being within the normal range (P=ns). Dietary and lifestyle management affected the EV profile, with lower signals observed from platelet- and endothelial cell-derived EVs (P<0.05) as well as FABP4-, TNFα- and Interferon ϒ-expressing EVs at 6 months’ follow-up (P<0.05, P=0.05, P=0.06, respectively). The exosomal marker CD9 correlated with FABP4, interferon γ, adiponectin and TNFα (r=0.49, r=0.41, r=0.59, r=0.53, all P<0.05), suggesting that exosomes are the main carrier of these adipokines.

Conclusion: EVs can be regarded as diverse biological vectors playing an important role in regulation of adipose tissue homeostasis and inflammatory processes. Their concentration, cellular origin and content do not directly correlate with BMI but are affected by gender and the presence of obesity-driven comorbidities.