Résumé
Background: Obesity-associated metabolic dysfunctions have been linked to dysregulated production of secreted factors from adipose tissue, known as adipocytokines. Besides, accumulating evidences suggest a role for fat-derived extracellular vesicles (EV) in the development of metabolic disturbances. Since EV convey numerous proteins and metabolites, we aimed to evaluate their contribution in the secretion of adipocytokines. Methods: Plasma samples collected from patients suffering of metabolic syndrome were used to isolate EV subtypes, namely microvesicles (MV) and exosomes (EXO) by differential centrifugations. Patients were classified according to their body mass index (BMI): Control (BMI < 27), overweight (2730). 22 adipocytokines circulating concentrations were successively measured on total, MV- and EV-depleted plasma samples by multiplex immunoassays. Results: MV and EXO populations, respectively, quantified by flow cytometry and NTA, were significantly increased with BMI supporting a role of these vesicles as metabolic relays in the context of obesity. Multiplex analysis of plasma adipocytokines confirms dysregulated production of these factors with increased BMI. Sequential depletion of MV and EXO from all plasma patients did not modify adipocytokine plasma levels, at the exception of MIF (macrophage migration inhibitory factor). Importantly, MIF plasma concentration was decreased by half following MV depletion and this MV-associated proportion was unchanged with obesity. Specific association of MIF with MV was observed in purified MV from different cell sources, including adipocytes and lymphocytes, demonstrating that this adipocytokine uses MV as a constitutive secretory pathway. Finally, we demonstrated that MV-associated MIF was able to mediate functional responses such as ERK activation in macrophages. Summary/Conclusion: All together, our study emphasizes the importance to consider the MV secretory pathway in the metabolic actions of MIF adipocytokine.