Resveratrol Suppresses PAI-1 Gene Expression in a Human In Vitro Model of Inflamed Adipose Tissue

被引:30
作者
Zagotta, Ivana [1 ]
Dimova, Elitsa Y. [2 ,3 ]
Funcke, Jan-Bernd [1 ]
Wabitsch, Martin [1 ]
Kietzmann, Thomas [2 ,3 ]
Fischer-Posovszky, Pamela [1 ]
机构
[1] Univ Ulm, Med Ctr, Dept Pediat & Adolescent Med, Div Pediat Endocrinol & Diabet, D-89075 Ulm, Germany
[2] Univ Oulu, Dept Biochem, Oulu 90014, Finland
[3] Univ Oulu, Bioctr Oulu, Oulu 90014, Finland
基金
芬兰科学院;
关键词
PLASMINOGEN-ACTIVATOR INHIBITOR-1; NF-KAPPA-B; INDUCIBLE FACTOR-I; HIGH-FAT DIET; PROTEIN-KINASE; IMPAIRED FIBRINOLYSIS; CALORIE RESTRICTION; INSULIN SENSITIVITY; HEMOSTATIC FACTORS; METABOLIC SYNDROME;
D O I
10.1155/2013/793525
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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 NF kappa B pathway. Together, resveratrol can act as NF kappa B 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.
引用
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页数:13
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