Angiogenesis inhibitor, TNP-470, prevents diet-induced and genetic obesity in mice
Angiogenesis inhibitor, TNP-470, prevents diet-induced and genetic obesity in mice
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DOI：
10.1161/01.res.0000132745.76882.70
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发表时间：
2004-06-25
影响因子：
20.1
通讯作者：
Cao, YH
中科院分区：
文献类型：
--
作者：
Bråkenhielm, E;Cao, RH;Cao, YH
已提出脂肪组织生长涉及新血管的募集。在这里，我们测试了一个假设，即在小鼠体内输送血管生成抑制剂可以预防饮食引起的肥胖，这是人类最常见的肥胖类型。我们发现，全身施用选择性血管生成抑制剂 TNP-470 (AGM-1470) 可预防高热量饮食喂养的 wt 小鼠以及遗传瘦素缺陷的 ob/ob 小鼠的肥胖。 TNP-470 对小鼠肥胖的抑制涉及脂肪组织中血管的减少。这种治疗策略似乎选择性地影响脂肪组织的生长，这是通过总脂肪与去脂体重之间的比率来衡量的。有趣的是，TNP-470 治疗可降低血清低密度脂蛋白胆固醇水平。此外，胰岛素水平降低，表明胰岛素敏感性增加，表明血管生成抑制剂可以预防 II 型糖尿病的发展。我们的研究结果表明，与其他组织的生长和器官发生类似，脂肪组织的生长依赖于血管生成。我们的观察结果可能对预防肥胖和相关疾病具有概念意义。
Adipose tissue growth has been proposed to involve recruitment of new blood vessels. Here, we test the hypothesis that delivery of an angiogenesis inhibitor in mice may prevent diet-induced obesity, the most common type of obesity in humans. We show that systemic administration of a selective angiogenesis inhibitor, TNP-470 (AGM-1470), prevents obesity in high caloric diet-fed wt mice as well as in genetically leptin-deficient ob/ob mice. Inhibition of obesity in mice by TNP-470 involves a reduction of vascularity in the adipose tissue. This therapeutic strategy appears to selectively affect the growth of adipose tissue as measured by the ratio between total fat and lean body mass. Interestingly, the treatment with TNP-470 results in decreased serum levels of low-density lipoprotein cholesterol. Furthermore, insulin levels are reduced, which indicates increased insulin sensitivity, suggesting that angiogenesis inhibitors may prevent the development of type II diabetes. Our findings suggest that similarly to growth and organogenesis in other tissues, adipose tissue growth is dependent on angiogenesis. Our observations may have conceptual implications for the prevention of obesity and related disorders.