Extracellular Vesicles from Hypoxic Adipocytes and Obese Subjects Reduce Insulin-Stimulated Glucose Uptake

We investigate the effects of extracellular vesicles (EVs) obtained from in vitro adipocyte cell models and from obese subjects on glucose transport and insulin responsiveness. Methods and results: EVs are isolated from the culture supernatant of adipocytes cultured under normoxia, hypoxia (1% oxygen), or exposed to macrophage conditioned media (15% v/v). EVs are isolated from the plasma of lean individuals and subjects with obesity. Cultured adipocytes are incubated with EVs and activation of insulin signalling cascades and insulin-stimulated glucose transport are measured. EVs released from hypoxic adipocytes impair insulin-stimulated 2-deoxyglucose uptake and reduce insulin mediated phosphorylation of AKT. Insulin-mediated phosphorylation of extracellular regulated kinases (ERK1/2) is not affected. EVs from individuals with obesity decrease insulin stimulated 2-deoxyglucose uptake in adipocytes (p = 0.0159). Conclusion: EVs released by stressed adipocytes impair insulin action in neighboring adipocytes ; J.M. and F.J.O. contributed equally to this wortk. J.M. was a joint Ph.D student between University of Liverpool and CICbioGUNE. F.J.O. was supported by the foundation Daniel Bravo. Funding: MINECO (SAF2015‐66312) to J.M.F.P., Fondo Europeo de Desarrollo Regional (FEDER) and CIBER obesidad (CIBERobn), Instituto de Salud Carlos III to J.M.F.R. J.M., F.J.O., and S.M. performed data acquisition and analysis; J.M., F.J.O., J.M.F.P., M.W., J.M.F.R., and S.M. performed writing of manuscript