Alessi Marie-Christine, Poggi Marjorie, Juhan-Vague Irène
Laboratoire d'hématologie-Inserm UMR 626, Faculty of Medicine, Marseilles, France.
Curr Opin Lipidol. 2007 Jun;18(3):240-5. doi: 10.1097/MOL.0b013e32814e6d29.
Plasminogen activator inhibitor (PAI)-1 is a physiological inhibitor of plasminogen activators (urokinase and tissue types) and vitronectin. It is synthesized by adipose tissue, and its levels in plasma are increased in obesity and reduced with weight loss. Circulating PAI-1 level predicts development of type 2 diabetes, suggesting that it may be causally related to development of obesity. A role for PAI-1 in development of obesity has only partially been established, however. This review summarizes current knowledge, gives context to developments thus far and discusses controversies.
In addition to its role in atherothrombosis, PAI-1 might be involved in adipose tissue development. PAI-1 is produced by ectopic fat depots under the influence of inducers. Among the most recently described inducers are inflammation, oxidative stress and circadian clock protein. PAI-1 may play several roles in contributing to obesity: through indirect effects on insulin signalling, by influencing adipocyte differentiation and by regulating recruitment of inflammatory cells within adipose tissue.
These recent findings emphasize the involvement of PAI-1 in controlling the biology of adipose tissue; PAI-1 is an attractive new therapeutic target to retard the metabolic complications that accompany obesity.
纤溶酶原激活物抑制剂（PAI）-1是纤溶酶原激活物（尿激酶型和组织型）及玻连蛋白的生理性抑制剂。它由脂肪组织合成，血浆中其水平在肥胖时升高，体重减轻时降低。循环PAI-1水平可预测2型糖尿病的发生，提示其可能与肥胖的发生存在因果关系。然而，PAI-1在肥胖发生中的作用仅部分得到证实。本综述总结了当前的知识，阐述了迄今为止的研究进展并讨论了争议之处。
除了在动脉粥样硬化血栓形成中的作用外，PAI-1可能还参与脂肪组织发育。PAI-1在诱导剂的影响下由异位脂肪储存产生。最近描述的诱导剂包括炎症、氧化应激和昼夜节律蛋白。PAI-1可能通过对胰岛素信号传导的间接影响、影响脂肪细胞分化以及调节脂肪组织内炎症细胞的募集等多种作用导致肥胖。
这些最新发现强调了PAI-1在控制脂肪组织生物学方面的作用；PAI-1是延缓肥胖相关代谢并发症的一个有吸引力的新治疗靶点。
