• J H N Lindeman, H Pijl, K Toet, P H C Eilers, B van Ramshorst, M M Buijs, J H van Bockel, and T Kooistra.
• Department of Vascular Surgery, Leiden University Medical Center, Leiden, The Netherlands. Lindeman@lumc.nl
• Int J Obes (Lond). 2007 Nov 1; 31 (11): 1671-9.

ObjectiveThe 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.DesignA comprehensive approach comprising observational, in vitro, and human intervention studies.Measurements And ResultsWe 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.ConclusionOur 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.

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