Angiopoietin-like Protein 2 Promotes Chronic Adipose Tissue Inflammation and Obesity-Related Systemic Insulin Resistance
Angiopoietin-like Protein 2 Promotes Chronic Adipose Tissue Inflammation and Obesity-Related Systemic Insulin Resistance
复制标题
DOI：
10.1016/j.cmet.2009.08.003
复制
发表时间：
2009-09-02
期刊：
影响因子：
29
通讯作者：
Oike, Yuichi
中科院分区：
文献类型：
--
作者：
Tabata, Mitsuhisa;Kadomatsu, Tsuyoshi;Oike, Yuichi
最近的肥胖研究为胰岛素抵抗和代谢失调的机制提供了新的见解。已经做出了许多努力来确定肥胖相关的脂肪组织炎症和胰岛素抵抗的关键调节因子。我们发现血管生成素样蛋白2（Angptl 2）由脂肪组织分泌，并且其循环水平与小鼠和人类的肥胖、全身性胰岛素抵抗和炎症密切相关。Angptl 2通过整合素信号传导激活内皮细胞中的炎性级联反应并诱导单核细胞/巨噬细胞的趋化性。体内组成性Angptl 2活化诱导脉管系统的炎症，其特征在于白细胞大量附着于血管壁和增加的渗透性。在饮食诱导的肥胖小鼠中，Angptl 2缺失改善脂肪组织炎症和全身胰岛素抵抗。相反，脂肪组织中的Angptl 2过表达引起非肥胖小鼠的局部炎症和全身胰岛素抵抗。因此，Angptl 2是将肥胖与全身性胰岛素抵抗联系起来的关键脂肪细胞衍生的炎症介质。
Recent studies of obesity have provided new insights into the mechanisms underlying insulin resistance and metabolic dysregulation. Numerous efforts have been made to identify key regulators of obesity-linked adipose tissue inflammation and insulin resistance. We found that angiopoietin-like protein 2 (Angptl2) was secreted by adipose tissue and that its circulating level was closely related to adiposity, systemic insulin resistance, and inflammation in both mice and humans. Angptl2 activated an inflammatory cascade in endothelial cells via integrin signaling and induced chemotaxis of monocytes/macrophages. Constitutive Angptl2 activation in vivo induced inflammation of the vasculature characterized by abundant attachment of leukocytes to the vessel walls and increased permeability. Angptl2 deletion ameliorated adipose tissue inflammation and systemic insulin resistance in diet-induced obese mice. Conversely, Angptl2 overexpression in adipose tissue caused local inflammation and systemic insulin resistance in nonobese mice. Thus, Angptl2 is a key adipocyte-derived inflammatory mediator that links obesity to systemic insulin resistance.