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.
Design:
A comprehensive approach comprising observational, in vitro, and human intervention studies.
Measurements and 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-α, IL-1 or transforming growth factor-β 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.
Conclusion:
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.
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Acknowledgements
We thank Professor Hans Romijn for his helpful comments during the preparation of the paper. This work was supported by The Netherlands Heart Foundation (NHS 1997-100).
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Lindeman, J., Pijl, H., Toet, K. et al. Human visceral adipose tissue and the plasminogen activator inhibitor type 1. Int J Obes 31, 1671–1679 (2007). https://doi.org/10.1038/sj.ijo.0803650
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DOI: https://doi.org/10.1038/sj.ijo.0803650