Human adipocyte extracellular vesicles in reciprocal signaling between adipocytes and macrophages

OBJECTIVE:

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.

DESIGN AND METHODS:

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.

RESULTS:

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.

CONCLUSIONS:

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.

Authors: 
M.E. Kranendonk, F.L. Visseren, B.W. van Balkom, E.N. Hoen, J.A. van Herwaarden, W. de Jager, H.S. Schipper, A.B. Brenkman, M.C. Verhaar, M.H. Wauben, E. Kalkhoven
Authors from the NMC: 
DOI: 
10.1002/oby.20679
Pages: 
2013; [Epub ahead of print]
Published in: 
Obesity
Date of publication: 
December, 2013
Status of the publication: 
Published/accepted