Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics and Adolescent Medicine, Ulm University Medical Center, Ulm, Germany.
Oxid Med Cell Longev. 2013;2013:793525. doi: 10.1155/2013/793525. Epub 2013 Jun 2.
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.
纤溶酶原激活物抑制剂-1（PAI-1）水平升高与许多病理生理并发症有关；其中包括肥胖症。白藜芦醇被提议改善与肥胖相关的健康问题，但白藜芦醇对肥胖症中 PAI-1 基因表达的影响尚不完全清楚。在这项研究中，我们使用 SGBS 脂肪细胞和人脂肪组织炎症模型来研究白藜芦醇对 PAI-1 产生的影响。白藜芦醇处理 SGBS 脂肪细胞可使 PAI-1 mRNA 和蛋白的表达呈时间和浓度依赖性降低。进一步的实验表明，与肥胖相关的炎症条件会导致 PAI-1 基因表达上调，而白藜芦醇则拮抗了这种上调。尽管在非炎症条件下，PI3K、Sirt1、AMPK、ROS 和 Nrf2 信号通路似乎在调节 PAI-1 基因表达中发挥了重要作用，但这些信号通路成分并未参与介导白藜芦醇对 PAI-1 产生的影响在炎症条件下。相反，我们证明，白藜芦醇在炎症条件下对 PAI-1 诱导的作用是通过抑制 NF κ B 通路介导的。总之，白藜芦醇可以作为脂肪细胞中的 NF κ B 抑制剂，因此炎症脂肪组织中 PAI-1 表达的降低可能为肥胖症的新治疗选择提供新的思路。
