Hindawi Publishing Corporation Oxidative Medicine and Cellular Longevity Volume 2013, Article ID 793525, 13 pages http://dx.doi.org/10.1155/2013/793525 Research Article Resveratrol Suppresses PAI-1 Gene Expression in a Human In Vitro Model of Inflamed Adipose Tissue Ivana Zagotta, 1 Elitsa Y. Dimova, 2 Jan-Bernd Funcke, 1 Martin Wabitsch, 1 Thomas Kietzmann, 2 and Pamela Fischer-Posovszky 1 1 Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics and Adolescent Medicine, Ulm University Medical Center, Eythstraße 24, 89075 Ulm, Germany 2 Department of Biochemistry and Biocenter Oulu, University of Oulu, P.O.B. 3000, 90014 Oulu, Finland Correspondence should be addressed to Tomas Kietzmann; tkietzm@gwdg.de and Pamela Fischer-Posovszky; pamela.fscher@uniklinik-ulm.de Received 22 March 2013; Revised 7 May 2013; Accepted 8 May 2013 Academic Editor: Nilanjana Maulik Copyright © 2013 Ivana Zagotta et al. Tis 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 efect 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 infammation to examine the efects 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 infammatory 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 signifcant role in the modulation of PAI-1 gene expression under noninfammatory conditions, those signaling components were not involved in mediating the resveratrol efects on PAI-1 production under infammatory conditions. Instead, we demonstrate that the resveratrol efects on PAI-1 induction under infammatory conditions were mediated via inhibition of the NFB pathway. Together, resveratrol can act as NFB inhibitor in adipocytes and thus the subsequently reduced PAI-1 expression in infamed adipose tissue might provide a new insight towards novel treatment options of obesity. 1. Introduction Obesity is becoming an increasing public health problem worldwide. Te excessive accumulation of adipose tissue leads to the development of dyslipidemia, impaired glucose metabolism, hypertension, and proinfammation, processes playing an essential role in the pathogenesis of cardiovas- cular disease, type 2 diabetes, the metabolic syndrome, and various cancers (reviewed by [1]). Many of those obesity- related pathophysiological conditions are associated with increased plasminogen activator inhibitor-1 (PAI-1) levels [2–6]. PAI-1 is the primary, fast-acting inhibitor of both tissue-type and urokinase-type plasminogen activators and therefore controls the regulation of the fbrinolytic system in blood [7, 8]. In addition, PAI-1 is an important regulator of extracellular matrix turnover, tissue remodeling, and fbrosis [9]. PAI-1 levels can be increased in response to hypoxia [10, 11], hormones like insulin [12, 13], coagulation factors, and cytokines (discussed by [14]). More recently PAI-1 levels have been considered as one of the biomarkers used to predict obesity-associated diseases [15]. Elevated PAI-1 mRNA levels have been found in adipose tissues from obese ob/ob mice [16] and also in human obesity with higher expression levels in visceral compared to subcutaneous adipose tissue depots [17]. Tus, high plasma PAI-1 levels are a common fnding in obesity in both mice and humans [18–25]. Most importantly, the obesity-induced PAI-1 increase is reversible by lifestyle intervention. Weight loss due to calorie restriction decreased plasma PAI-1 concentrations in obese individuals [26, 27]. Tese data imply that substances that potentially mimic calorie restriction may be used as modulators of PAI-1 levels in the treatment of obesity and obesity-related diseases.