Abstract
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 κ B pathway. Together, resveratrol can act as NF κ 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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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AMP-Activated Protein Kinases / metabolism
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Adipocytes / drug effects
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Adipocytes / enzymology
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Adipocytes / pathology
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Adipose Tissue / metabolism
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Adipose Tissue / pathology
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Animals
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Arrhythmias, Cardiac / genetics
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Arrhythmias, Cardiac / pathology
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Culture Media, Conditioned / pharmacology
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DNA / metabolism
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Down-Regulation / drug effects
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Down-Regulation / genetics
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Female
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Gene Expression Regulation / drug effects*
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Genetic Diseases, X-Linked / genetics
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Genetic Diseases, X-Linked / pathology
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Gigantism / genetics
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Gigantism / pathology
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Heart Defects, Congenital / genetics
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Heart Defects, Congenital / pathology
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Humans
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Inflammation / enzymology
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Inflammation / genetics*
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Intellectual Disability / genetics
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Intellectual Disability / pathology
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Mice
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Models, Biological*
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NF-E2-Related Factor 2 / metabolism
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NF-kappa B / metabolism
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Phosphatidylinositol 3-Kinases / metabolism
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Plasminogen Activator Inhibitor 1 / genetics*
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Plasminogen Activator Inhibitor 1 / metabolism
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Protein Binding / drug effects
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Reactive Oxygen Species / metabolism
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Resveratrol
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Sirtuin 1 / metabolism
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Stilbenes / pharmacology*
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Time Factors
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Up-Regulation / drug effects
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Up-Regulation / genetics
Substances
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Culture Media, Conditioned
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NF-E2-Related Factor 2
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NF-kappa B
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Plasminogen Activator Inhibitor 1
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RNA, Messenger
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Reactive Oxygen Species
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Stilbenes
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DNA
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Phosphatidylinositol 3-Kinases
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AMP-Activated Protein Kinases
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Sirtuin 1
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Resveratrol
Supplementary concepts
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Simpson-Golabi-Behmel syndrome