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

Abstract

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 6months 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 γ, interleukin-6, TNF-α) and adipocyte marker (adiponectin, FABP4, PPARγ) 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 γ, IL-6, TNF-α, adiponectin, PPARγ or CD9. EV-derived fatty acid binding protein 4 (FABP4) increased at 1month (+49%) before returning to baseline by 6months (-51%, p<0.05), corresponding to similar changes in circulating plasma FABP4 (+22 and -24% at 1 and 6months, respectively; p<0.001). Patients who underwent biliopancreatic diversion had lower FABP4-expressing EVs at 6months 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-α and interferon γ (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.