Extracellular vesicles (EVs) released by human adipocytes or adipose tissue (AT)‐explants play a role in the paracrine interaction between adipocytes and macrophages, a key mechanism in AT inflammation, leading to metabolic complications like insulin resistance (IR) were determined.

EVs released from in vitro differentiated adipocytes and AT‐explants ex vivo were characterized by electron microscopy, Western blot, multiplex adipokine‐profiling, and quantified by flow cytometry. Primary monocytes were stimulated with EVs from adipocytes, subcutaneous (SCAT) or omental‐derived AT (OAT), and phenotyped. Macrophage supernatant was subsequently used to assess the effect on insulin signaling in adipocytes.

Adipocyte and AT‐derived EVs differentiated monocytes into macrophages characteristic of human adipose tissue macrophages (ATM), defined by release of both pro‐ and anti‐inflammatory cytokines. The adiponectin‐positive subset of AT‐derived EVs, presumably representing adipocyte‐derived EVs, induced a more pronounced ATM‐phenotype than the adiponectin‐negative AT‐EVs. This effect was more evident for OAT‐EVs versus SCAT‐EVs. Furthermore, supernatant of macrophages pre‐stimulated with AT‐EVs interfered with insulin signaling in human adipocytes. Finally, the number of OAT‐derived EVs correlated positively with patients HOMA‐IR.

A possible role for human AT‐EVs in a reciprocal pro‐inflammatory loop between adipocytes and macrophages, with the potential to aggravate local and systemic IR was demonstrated.