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New Animal Models Of Leaness And Obesity by Genetic Engineering and its Application to Therapy

基因工程瘦和肥胖的新动物模型及其在治疗中的应用

基本信息

批准号：
09557080
负责人：
NAKAO Kazuwa
金额：
$ 7.3万
依托单位：
KYOTO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1998
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09557080/
关键词：
leptin transgenic mouse obesity food inake energy expenditure white adipose tissue insulin sensitivity leaness 脂肪組織体重摂食量

项目摘要

(Purpose) Disorders in regulation of energy metabolism lead to diabetes and obesity. Since diabetes and obesity are main risk factors of caridovascular diseases, elucidation of pathophysilogy of obesity and development of drugs are important. In the present study, in order to elucidate regulation of energy metabolism, we developed transgenic mice in a molecule of energy metabolism. We created transgenic mice overexpressing leptin in the liver, and examined chronic action of leptin.(Methods) We created transgenic mice by microinjection of vector in which leptin cDNA is under the control of serum amyloid component P promoter, which is specific in the liver to eggs of BDF1 mice. We examined food intake, body weight, and body temperature.(Results) Circulating leptin levels in the leptin-transgenic mice (Tg mice) are approximately 100ng/ml, about 10-fold of those of control mice. The Tg mice are approximately 70 % of the control mice in weight, and fat less as white and brown adipose tissues are mostly absent. Increase of insulin sensitivity were observed in IPGTT and IPIIT.Furthermore, increase of body temperature by 1.5-2 。C and significant elevation of systemic blood pressure (119.2 * 2.3 vs. 102.6 * 2.6 mmHg, P < 0.001) are noted.(Discussion) In the present study, we succeeded in creating leptin transgenic mice, in which circulating leptin levels are 10-fold of the control mice. The Tg mice are 70 % in body weight as compared with the control mice, are fatless. The increase of body temperature indictates the involvement of leptin in energy expenditure. The Tg mice are considered to be a good model for the study of chronic action of leptin, and are a new animal model of leaness. The study of post-leptin signal of regulation in energy metabolism will lead to the understanding of overall feature of molecules in energy metabolism.

（目的）能量代谢调节障碍导致糖尿病和肥胖症。由于糖尿病和肥胖是心血管疾病的主要危险因素，阐明肥胖的病理生理和药物的开发是重要的。在本研究中，为了阐明能量代谢的调节，我们开发了能量代谢分子的转基因小鼠。我们建立了在肝脏中过度表达瘦素的转基因小鼠，并检查了瘦素的慢性作用。（方法）将瘦素cDNA置于血清淀粉样蛋白P启动子的控制下，通过显微注射的方法建立转基因小鼠。血清淀粉样蛋白P启动子在BDF 1小鼠肝脏中对卵子具有特异性。我们检查了食物摄入量、体重和体温。（结果）瘦素转基因小鼠（Tg小鼠）的循环瘦素水平约为100 ng/ml，约为对照组的10倍。Tg小鼠的体重约为对照小鼠的70%，并且脂肪较少，因为白色和棕色脂肪组织大多不存在。IPGTT和IPIIT组胰岛素敏感性增加，体温升高1.5-2。C和体循环血压显著升高（119.2 * 2.3vs.102.6 * 2.6mmHg，P < 0.001）。（讨论）在本研究中，我们成功地创建了瘦素转基因小鼠，其中循环瘦素水平是对照小鼠的10倍。与对照小鼠相比，Tg小鼠的体重为70%，是无脂肪的。体温升高提示瘦素参与能量消耗。Tg小鼠是研究瘦素慢性作用的良好模型，是一种新的瘦素动物模型。研究瘦素后信号在能量代谢中的调节作用，有助于了解能量代谢分子的整体特征。