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Obesity and impaired fibrinolysis: role of adipose production of plasminogen activator inhibitor-1

International Journal of Obesity volume 28, pages 1357–1364 (2004)Cite this article

Abstract

Obesity is the central promoter of the metabolic syndrome which also includes disturbed fibrinolysis in addition to hypertension, dyslipidaemia and impaired glucose tolerance/type 2 diabetes mellitus. Plasminogen activator inhibitor-1 (PAI-1) is the most important endogenous inhibitor of tissue plasminogen activator and uro-plasminogen activator, and is a main determinant of fibrinolytic activity. There is now compelling evidence that obesity and, in particular, an abdominal type of body fat distribution are associated with elevated PAI-1 antigen and activity levels. Recent studies established that PAI-1 is expressed in adipose tissue. The greater the fat cell size and the adipose tissue mass, the greater is the contribution of adipose production to circulating PAI-1. Experimental data show that visceral adipose tissue has a higher capacity to produce PAI-1 than subcutaneous adipose tissue. Studies in human adipocytes indicate that PAI-1 synthesis is upregulated by insulin, glucocorticoids, angiotensin II, some fatty acids and, most potently, by cytokines such as tumour necrosis factor-α and transforming growth factor-β, whereas catecholamines reduce PAI-1 production. Interestingly, pharmacological agents such as thiazolidinediones, metformin and AT1-receptor antagonists were found to reduce adipose expression of PAI-1. In addition, weight loss by dietary restriction or comprehensive lifestyle modification is effective in lowering PAI-1 plasma levels. In conclusion, impaired fibrinolysis in obesity is probably also due to an increased expression of PAI-1 in adipose tissue. An altered function of the endocrine system and an impaired auto-/paracrine function at the fat cell levels may mediate this disturbance of the fibrinolytic system and thereby increase the risk for cardiovascular disease.

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  1. Else Kröner-Fresenius-Centre for Nutritional Medicine, Technical University of Munich, Freising-Weihenstephan, Germany

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Skurk, T., Hauner, H. Obesity and impaired fibrinolysis: role of adipose production of plasminogen activator inhibitor-1. Int J Obes 28, 1357–1364 (2004). https://doi.org/10.1038/sj.ijo.0802778

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