Bariatric Surgery Is Accompanied by Changes in Extracellular Vesicle-Associated and Plasma Fatty Acid Binding Protein 4

Bariatric surgery markedly reduces fat mass with beneficial effects on cardiometabolic health but the mechanisms involved are not fully understood. Extracellular vesicles (EVs) are secreted by a variety of cells, including adipocytes, and may mediate some of these benefits. However, the effects of bariatric surgery on circulating EVs are unclear. Concentration of plasma EVs isolated by ultracentrifugation at baseline, 1 and 6 months post-bariatric surgery (n = 20) was established using Nanoparticle Tracking Analysis. EV origin (CD9: exosome; CD41: platelet; CD235a: erythrocyte; CD11b: leukocyte; CD144: endothelial), cytokine (interferon gamma, interleukin-6, TNF-alpha) and adipocyte marker (adiponectin, FABP4, PPAR gamma) expression was measured by time-resolved fluorescence immunoassay. EV concentration and cell-of-origin markers (CD41, CD235a, CD11b, CD144) did not alter in response to surgery, neither did EV-expressed interferon gamma, IL-6, TNF-alpha, adiponectin, PPAR gamma or CD9. EV-derived fatty acid binding protein 4 (FABP4) increased at 1 month (+ 49%) before returning to baseline by 6 months (- 51%, p < 0.05), corresponding to similar changes in circulating plasma FABP4 (+ 22 and - 24% at 1 and 6 months, respectively; p < 0.001). Patients who underwent biliopancreatic diversion had lower FABP4-expressing EVs at 6 months compared to those who underwent sleeve gastrectomy/gastric banding (p < 0.05), despite similar percentage weight reduction (- 19 vs - 20%, respectively). CD9 expression correlated with EV-expressed FABP4, adiponectin, TNF-alpha and interferon gamma (r = 0.5, r = 0.59, r = 0.53, r = 0.41, respectively, p < 0.005), suggesting transport by an EV population of exosomal rather than microvesicular origin. Bariatric surgery leads to a transient change in circulating EV- and plasma-derived FABP4, reflecting alterations in adipose tissue homeostasis.