title: Human visceral adipose tissue and the plasminogen activator inhibitor type 1.
abstract: OBJECTIVE
  The objective of this study was to systematically evaluate the molecular basis of the association between visceral fat mass and plasma plasminogen activator inhibitor-1 (PAI-1) levels in man.
  
  
  METHODS
  A comprehensive approach comprising observational, in vitro, and human intervention studies.
  
  
  RESULTS
  We confirmed an exclusive relationship between visceral fat and plasma PAI-1 levels (r=0.79, P<0.001) and corroborated preferential PAI-1 release from adipose tissue explants. Yet, messenger RNA analysis and in vivo measurement of PAI-1 release from visceral fat (AV-differences over the omentum) not only excluded visceral adipose tissue as a relevant source of circulating PAI-1, but also excluded visceral fat as a significant source of proinflammatory mediators such as tumor necrosis factor-alpha, IL-1 or transforming growth factor-beta that could induce PAI-1 expression in tissues other than visceral fat. Short-term interventions with acipimox and growth hormone (GH) as well as statistical evaluation excluded free fatty acids and GH as metabolic links. Further analysis of the metabolic data in a stepwise regression model indicated that plasma PAI-1 levels and visceral fat rather are co-correlates that both relate to impaired lipid handling.
  
  
  CONCLUSIONS
  Our PAI-1 studies show that visceral fat mass and plasma PAI-1 levels are co-correlated rather than causatively related, with lipid load as common denominator.
authors.affiliation: Department of Vascular Surgery, Leiden University Medical Center, Leiden, The Netherlands. Lindeman@lumc.nl
authors.forename: J H N
authors.initials: JH
authors.lastname: Lindeman
authors.forename: H
authors.initials: H
authors.lastname: Pijl
authors.forename: K
authors.initials: K
authors.lastname: Toet
authors.forename: P H C
authors.initials: PH
authors.lastname: Eilers
authors.forename: B
authors.initials: B
authors.lastname: van Ramshorst
authors.forename: M M
authors.initials: MM
authors.lastname: Buijs
authors.forename: J H
authors.initials: JH
authors.lastname: van Bockel
authors.forename: T
authors.initials: T
authors.lastname: Kooistra
mesh_terms: D050154:Adiposity / Q000502:physiology; D000328:Adult; D000886:Anthropometry; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D019382:Human Growth Hormone / Q000172:deficiency; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D050152:Intra-Abdominal Fat / Q000033:anatomy & histology / Q000378:metabolism* / Q000473:pathology; D050356:Lipid Metabolism; D008875:Middle Aged; D009765:Obesity / Q000378:metabolism / Q000473:pathology; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood* / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D046509:Tissue Culture Techniques; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; C051321:SERPINE1 protein, human; D014409:Tumor Necrosis Factor-alpha; D019382:Human Growth Hormone