Effects of extracellular vesicles released by hypoxic adipocytes in Insulin action

Abstract

Extracellular vesicles (EVs) are released by many cells and provide a mechanism for intercellular communication in an autocrine and paracrine fashion. EVs are also released during pathological states. Adipocytes release EVs, however, the impact of these vesicles in glucose metabolism and insulin action has not been thoroughly investigated. We sought to investigate whether EVs released by metabolically challenged adipocytes exposed to hypoxia or to macrophage conditioned media affect insulin responsiveness and glucose transport. EVs were isolated from the culture supernatant of adipocytes cultured under normoxia, hypoxia (1% oxygen) or exposed to macrophage conditioned media (15%v/v). EVs were isolated from plasma of lean and obese individuals. EVs were used to treat cells and glucose transport and activation of insulin signalling cascades was measured. EVs released from hypoxic adipocytes but not those released by adipocytes exposed to macrophage conditioned media impaired insulin‐stimulated 2‐deoxyglucose uptake and reduced insulin‐stimulated Ser473 phosphorylation of AKT. ERK signalling was intact. Insulin stimulated glucose transport in muscle cells was also inhibited. EVs from obese individuals decreased insulin stimulated 2‐deoxyglucose uptake in adipocytes (p=0.0159). EVs from obese subjects contained distinct miRNA signatures. These findings indicate that EVs released by stressed adipocytes impair insulin action.Support or Funding InformationUniversity of Livepool, MINECO and FEDERThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.