Resveratrol suppresses PAI-1 gene expression in a human in vitro model of inflamed adipose tissue
Zagotta, Ivana; Dimova, Elitsa Y.; Funcke, Jan-Bernd; Wabitsch, Martin; Kietzmann, Thomas; Fischer-Posovszky, Pamela
Ivana Zagotta, Elitsa Y. Dimova, Jan-Bernd Funcke, Martin Wabitsch, Thomas Kietzmann, and Pamela Fischer-Posovszky, “Resveratrol Suppresses PAI-1 Gene Expression in a Human In Vitro Model of Inflamed Adipose Tissue,” Oxidative Medicine and Cellular Longevity, vol. 2013, Article ID 793525, 13 pages, 2013. doi:10.1155/2013/793525
Copyright © 2013 Ivana Zagotta et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Increased plasminogen activator inhibitor-1 (PAI-1) levels are associated with a number of pathophysiological complications; among them is obesity. Resveratrol was proposed to improve obesity-related health problems, but the effect of resveratrol on PAI-1 gene expression in obesity is not completely understood. In this study, we used SGBS adipocytes and a model of human adipose tissue inflammation to examine the effects of resveratrol on the production of PAI-1. Treatment of SGBS adipocytes with resveratrol reduced PAI-1 mRNA and protein in a time- and concentration-dependent manner. Further experiments showed that obesity-associated inflammatory conditions lead to the upregulation of PAI-1 gene expression which was antagonized by resveratrol. Although signaling via PI3K, Sirt1, AMPK, ROS, and Nrf2 appeared to play a significant role in the modulation of PAI-1 gene expression under noninflammatory conditions, those signaling components were not involved in mediating the resveratrol effects on PAI-1 production under inflammatory conditions. Instead, we demonstrate that the resveratrol effects on PAI-1 induction under inflammatory conditions were mediated via inhibition of the NFκB pathway. Together, resveratrol can act as NFκB inhibitor in adipocytes and thus the subsequently reduced PAI-1 expression in inflamed adipose tissue might provide a new insight towards novel treatment options of obesity.
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