Human visceral adipose tissue and the plasminogen activator inhibitor type 1.
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.
Lindeman
J H N
JH
Department of Vascular Surgery, Leiden University Medical Center, Leiden, The Netherlands. Lindeman@lumc.nl
Pijl
H
H
Toet
K
K
Eilers
P H C
PH
van Ramshorst
B
B
Buijs
M M
MM
van Bockel
J H
JH
Kooistra
T
T
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
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