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。由于糖尿病和肥胖是心血管疾病的主要危险因素，因此阐明肥胖的病理生理学和开发药物对于阐明能量代谢的调节非常重要。我们在能量代谢分子中培养了转基因小鼠，我们创建了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）我们通过以下方法创建了转基因小鼠。显微注射瘦素 cDNA 受血清淀粉样蛋白成分 P 启动子控制的载体，该启动子在 BDF1 小鼠的肝脏中具有特异性。我们检查了食物摄入量、体重和体温。（结果）循环瘦素水平。瘦素转基因小鼠（Tg小鼠）约为100ng/ml，是对照小鼠的约10倍。Tg小鼠的体重约为对照小鼠的70%。脂肪较少，几乎没有白色和棕色脂肪组织，在IPGTT和IPIIT中观察到胰岛素敏感性增加。此外，体温增加1.5-2。注意到 C 和全身血压显着升高（119.2 * 2.3 vs. 102.6 * 2.6 mmHg，P < 0.001）。（讨论）在本研究中，我们成功创建了瘦素转基因小鼠，其中循环瘦素水平为 10-与对照小鼠相比，Tg小鼠的体重增加了70％，并且体温没有增加。表明瘦素参与能量消耗，Tg小鼠被认为是研究瘦素慢性作用的良好模型，并且是瘦素后能量代谢调节信号的研究的新动物模型。导致对能量代谢中分子的整体特征的理解。