Research of the regulation of adipase mass through angiogenesis induced by the endothelin system

我们的研究方案和结果的具体目的如下：1.阐明内皮细胞产生ET-1在脂肪组织生长中血管生成障碍的分子机制。8周龄WT和KO小鼠的氧耗量和呼吸商检查没有显著差异。植入射频遥测仪评估的运动活动和体温没有显著差异。根据小鼠体重调整后的食物消耗量在WT和KO小鼠中没有差异。与WT小鼠相比，内皮素-1缺陷小鼠的血管密度降低，这表明KO小鼠脂肪生长受阻与血管形成减少相关。检测ET-1 KO小鼠的抗肥胖表型是否导致肥胖相关疾病的预防，我们发现血管内皮细胞中缺乏内皮素-1的小鼠抵抗饮食诱导的肥胖、高血压和胰岛素抵抗的发展。为探讨内皮素系统作为肥胖及相关疾病治疗靶点的可能性，将ET-1KO小鼠与遗传性肥胖和胰岛素抵抗小鼠模型交配，产生双突变小鼠。我们使用了两种不同的肥胖模型，ob/ob和KKAy小鼠。我们证明内皮素-1在诱导脂肪组织炎症中起着重要作用。

Our Specific Aims of the research proposal and Results obtained were as follows:1. To elucidate the molecular mechanisms of ET-1 produced from endothelial cell in impaired angiogenesis in adipose tissue growth.Examination of oxygen consumption and respiratory quotient at 8 weeks of age showed no significant differences between WT and KO mice. There were no significant differences in locomotor activity and body temperature assessed by implanted radio frequency telemetry. Food consumption adjusted for mouse weight was not different between WT and KO mice. Vascular density in endothelin-1 deficient mice was decreased as compared to WT mice, indicating that retarded adipose mass growth in KO mice correlated with decreased vascular formation.2. To examine whether anti-obesity phenotype in ET-1 KO mice leads to the prevention for obesity-related disorders.We found that mice lacking endothelin-1 in vascular endothelial cells resist the development of diet-induced obesity, hypertension, and insulin resistance.3. To investigate the possibility whether the endothelin system could be a therapeutic target for obesity and the related disorders.ET-1 KO mice were mated with mice models of genetic obesity and insulin resistance to produce double mutant mice. We used two different kinds of obesity models, ob/ob and KKAy mice. We demonstrated that endothelin-1 has an important role for inducing inflammation in adipose tissue.