title: Human adipocyte extracellular vesicles in reciprocal signaling between adipocytes and macrophages.
abstract: 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.
  
  
  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: Department of Vascular Medicine, University Medical Center Utrecht (UMC Utrecht), Utrecht, The Netherlands; Section Metabolic Diseases, Molecular Cancer Research, UMC Utrecht, Utrecht, The Netherlands.
authors: Mariëtte E G
authors: ME
authors: Kranendonk
authors: Frank L J
authors: FL
authors: Visseren
authors: Bas W M
authors: BW
authors: van Balkom
authors: Esther N M
authors: EN
authors: Nolte-'t Hoen
authors: Joost A
authors: JA
authors: van Herwaarden
authors: Wilco
authors: W
authors: de Jager
authors: Henk S
authors: HS
authors: Schipper
authors: Arjan B
authors: AB
authors: Brenkman
authors: Marianne C
authors: MC
authors: Verhaar
authors: Marca H M
authors: MH
authors: Wauben
authors: Eric
authors: E
authors: Kalkhoven
mesh_terms: D017667:Adipocytes / Q000648:ultrastructure*; D054392:Adipokines / Q000378:metabolism; D052242:Adiponectin / Q000378:metabolism; D000273:Adipose Tissue / Q000378:metabolism; D002450:Cell Communication; D002454:Cell Differentiation; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology; D007249:Inflammation / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D008264:Macrophages / Q000378:metabolism*; D009000:Monocytes / Q000166:cytology / Q000378:metabolism; D009765:Obesity / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D054392:Adipokines; D052242:Adiponectin; D016207:Cytokines; D007155:Immunologic Factors; D007328:Insulin