文章基本信息

标题：Tumor necrosis factor α is a key component in the obesity-linked elevation of plasminogen activator inhibitor 1
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作者：Fahumiya Samad ; K. Teoman Uysal ; Sarah M. Wiesbrock 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：1999
卷号：96
期号：12
页码：6902-6907
DOI：10.1073/pnas.96.12.6902
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Obesity is associated with a cluster of abnormalities, including hypertension, insulin resistance, hyperinsulinemia, and elevated levels of both plasminogen activator inhibitor 1 (PAI-1) and transforming growth factor {beta} (TGF-{beta}). Although these changes may increase the risk for accelerated atherosclerosis and fatal myocardial infarction, the underlying molecular mechanisms remain to be defined. Although tumor necrosis factor (TNF-) has been implicated in the insulin resistance associated with obesity, its role in other disorders of obesity is largely unknown. In this report, we show that in obese (ob/ob) mice, neutralization of TNF- or deletion of both TNF receptors (TNFRs) results in significantly reduced levels of plasma PAI-1 antigen, plasma insulin, and adipose tissue PAI-1 and TGF-{beta} mRNAs. Studies in which exogenous TNF- was infused into lean mice lacking individual TNFRs indicate that TNF- signaling of PAI-1 in adipose tissue can be mediated by either the p55 or the p75 TNFR. However, TNF- signaling of TGF-{beta} mRNA expression in adipose tissue is mediated exclusively via the p55 TNFR. Our results suggest that TNF- is a common link between the insulin resistance and elevated PAI-1 and TGF-{beta} in obesity. The chronic elevation of TNF- in obesity thus may directly promote the development of the complex cardiovascular risk profile associated with this condition.