title: Conditioned media from (pre)adipocytes stimulate fibrinogen and PAI-1 production by HepG2 hepatoma cells.
abstract: BACKGROUND
  Obesity is associated with a prothrombotic state, which may contribute to the increased risk of thrombotic events.
  
  
  OBJECTIVE
  To assess the effects of (pre)adipocyte-derived adipokines on fibrinogen, plasminogen activator inhibitor-1 (PAI-1) and tissue factor (TF) production by hepatocytes.
  
  
  METHODS
  HepG2 hepatocytes were incubated with conditioned media (CM) derived from preadipocytes and adipocytes, which had been untreated or prestimulated with tumor necrosis factor (TNF)-α, interleukin (IL)-1β or IL-6. After 24 h, supernatants and cell lysates were harvested for measurement of fibrinogen, PAI-1 and TF.
  
  
  RESULTS
  (Pre)adipocyte CM significantly enhanced the production of PAI-1 by HepG2 cells 2.5- to 4.4-fold. CM from cytokine-stimulated (pre)adipocytes significantly induced fibrinogen secretion 1.5- to 4.2-fold. TF production was not affected by the CM. After specific depletion of TNF-α, IL-1β or IL-6 from the CM, IL-6 was shown to be the most prominent stimulus of fibrinogen secretion and IL-1β of PAI-1 secretion. In addition, fibrinogen, PAI-1 and tissue factor production was evaluated by direct stimulation of HepG2 cells with TNF-α, IL-1β or IL-6. IL-6 enhanced fibrinogen synthesis 4.3-fold (P<0.01), whereas IL-1β induced PAI-1 production 5.0-fold (P<0.01). Gene expression analyses showed that TNF-α and IL-1β stimulate the adipocyte expression of TNF-α, IL-1β and IL-6. Cytokine stimulation of adipocytes may thus have induced an inflammatory response, which may have stimulated fibrinogen and PAI-1 production by HepG2 cells more potently.
  
  
  CONCLUSIONS
  SGBS (pre)adipocytes release cytokines that increase the production of fibrinogen and PAI-1 by HepG2 cells. IL-6 and IL-1β produced by (pre)adipocytes were the strongest inducers of fibrinogen and PAI-1 secretion, respectively.
authors.affiliation: Department of Vascular Medicine, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: D R
authors.initials: DR
authors.lastname: Faber
authors.forename: E
authors.initials: E
authors.lastname: Kalkhoven
authors.forename: J
authors.initials: J
authors.lastname: Westerink
authors.forename: J J
authors.initials: JJ
authors.lastname: Bouwman
authors.forename: H M
authors.initials: HM
authors.lastname: Monajemi
authors.forename: F L J
authors.initials: FL
authors.lastname: Visseren