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

内皮素系统诱导血管生成调节脂肪酶质量的研究

• 批准号: 18590813
• 负责人: EMOTO Noriaki
• 金额: $ 2.47万
• 依托单位: Kobe University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18590813/
• 关键词: Endothelin; Obesity; Angiopenesis

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.

我们的研究计划的具体目的和取得的成果如下： 1．旨在阐明内皮细胞产生的ET-1在脂肪组织生长中血管生成受损中的分子机制。8周龄时的耗氧量和呼吸商检查显示WT和KO小鼠之间没有显着差异。通过植入射频遥测技术评估的运动活动和体温没有显着差异。根据小鼠体重调整的食物消耗在 WT 和 KO 小鼠之间没有差异。与WT小鼠相比，endothelin-1缺陷小鼠的血管密度降低，表明KO小鼠脂肪量生长迟缓与血管形成减少相关。2．检测ET-1 KO小鼠的抗肥胖表型是否可以预防肥胖相关疾病。我们发现血管内皮细胞中缺乏内皮素1的小鼠可以抵抗饮食引起的肥胖、高血压和胰岛素抵抗的发展。3．为了研究内皮素系统是否可以成为肥胖及相关疾病的治疗靶点的可能性。将ET-1 KO小鼠与遗传性肥胖和胰岛素抵抗的小鼠模型交配，产生双突变小鼠。我们使用了两种不同类型的肥胖模型，ob/ob 和 KKAy 小鼠。我们证明内皮素-1 在诱导脂肪组织炎症方面具有重要作用。

项目成果

The effects of a dual endothelia receptor antagonist, bosentan, on metabolic parameters in the patients with pulmonary hypertension

双重内皮受体拮抗剂波生坦对肺动脉高压患者代谢参数的影响

• 发表时间: 2007
• 作者: Iwasa;N.;Nakayama;K.;Miyagawa;K.;Nonaka;H.;Emoto;N
• 通讯作者: N

Inhibitory effect of insulin on vasopressin-induced intracellular calcium response is blunted in hyperinsulinemic hypertensive patients : role of membrane fatty acid composition.

胰岛素对加压素诱导的细胞内钙反应的抑制作用在高胰岛素血症高血压患者中减弱：膜脂肪酸成分的作用。

• 发表时间: 2006
• 期刊: Heart Vessels 21
• 作者: Maekawa;K;Tsujino;T;Saito;K;Kim;JI;Ikeda;Y;Emoto;N;Yokoyama;M;Emoto Norikai;Maekawa Kouichi
• 通讯作者: Maekawa Kouichi

Dissection of roles of ET-1 in cardiovascular system: lesion from genetically modified mice

解析 ET-1 在心血管系统中的作用：转基因小鼠的病变

• 发表时间: 2007
• 作者: Emoto;N
• 通讯作者: N

Circadian expression of clock genes in human peripheral leukocytes

• DOI: 10.1016/j.bbrc.2007.01.063
• 发表时间: 2007-03-23
• 期刊: BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
• 影响因子: 3.1
• 作者: Fukuya, Hiroyuki;Emoto, Noriaki;Yokoyama, Mitsuhiro
• 通讯作者: Yokoyama, Mitsuhiro

Attenuation of Diet-Induced Obesity, Hypertension and Insulin Resistance in Vascular Endothelial Endothelin-1 Knockout Mice

血管内皮素 1 敲除小鼠中饮食引起的肥胖、高血压和胰岛素抵抗的减轻

• 发表时间: 2006
• 作者: Iwasa;N
• 通讯作者: N