Study for therapeutic effect of hepatocyte specific Pten deficiency on severe obesity.

肝细胞特异性Pten缺乏症对重度肥胖症的治疗作用研究。

• 批准号: 20591041
• 负责人: OHSHIMA Shigetoshi
• 金额: $ 2.91万
• 依托单位: Akita University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20591041/
• 关键词: PTEN; 肥満; 遺伝子治療; Pten遺伝子; ob/obマウス; Ob; マウス; Obマウス

Our aim is to investigate whether hepatocyte-specific Pten deficiency can improve obesity in the leptin-deficient ob/ob mouse by activating lipogenesis in the liver. For this purpose, we have mated hepatocyte-specific Pten deficient mouse with leptin-deficient ob/ob mouse and established ob/ob/AlbCre/Pten^<flox/flox> mouse. ob/ob mice (ob/ob group), ob/ob/AlbCre/Pten^<flox/flox> mice (double KO group), AlbCre/Pten^<flox/flox> mice (KO group), Wild type mice (WT group) were sacrificed at 40 weeks just after weaning and measured body weight, fat tissue weight around testis or ovary, liver weight, triglyceride content in the liver, serum transaminase level and total ROS level in serum. Moreover we investigated Akt activation by western blot analysis and examined the expression of various genes especially related to β-oxidation by quantitative real-time PCR. The result is Hepatocyte-specific Pten deficiency improved obesity in the leptin-deficient ob/ob mouse by activating lipogenesis in the liver.

我们的目的是研究肝细胞特异性Pten缺乏是否可以通过激活肝脏中的脂肪生成来改善瘦素缺乏的ob/ob小鼠的肥胖。为此，我们将肝细胞特异性Pten缺陷小鼠与瘦素缺陷ob/ob小鼠交配，建立ob/ob/AlbCre/Pten^<flox/flox>小鼠。在刚断奶后40周处死ob/ob小鼠（ob/ob组）、ob/ob/AlbCre/Pten^<flox/flox>小鼠（双KO组）、AlbCre/Pten^<flox/flox>小鼠（KO组）、野生型小鼠（WT组），并测量体重、睾丸或卵巢周围的脂肪组织重量、肝脏重量、肝脏中的甘油三酯含量、血清转氨酶水平和血清中的总ROS水平。此外，我们通过蛋白质印迹分析研究Akt活化，并通过定量实时PCR检测各种基因的表达，特别是与β-氧化相关的基因。结果是肝细胞特异性Pten缺乏通过激活肝脏中的脂肪生成来改善瘦素缺乏的ob/ob小鼠的肥胖。

项目成果

肝細胞特異的Pten欠損によるレプチン欠損ob/obマウスの肥満の改善

通过肝细胞特异性 Pten 缺乏改善瘦素缺陷 ob/ob 小鼠的肥胖

• 发表时间: 2011
• 作者: 大嶋重敏,堀江泰夫,後藤隆,三浦光一,澁谷友美,佐藤亘,道免孝洋,姉崎有美子,山田育弘,鎌田健太郎,鈴木聡,大西洋英

Hepatocyte-specific Pten deficiency improves obesity in the leptin-deficient ob/ob mouse.

肝细胞特异性 Pten 缺乏可改善瘦素缺陷 ob/ob 小鼠的肥胖。

• 发表时间: 2011
• 作者: Shigetoshi Ohshima;Yasuo Horie;Takashi Goto;Kouichi Miura;Akira Suzuki;Hirohide Ohnishi
• 通讯作者: Hirohide Ohnishi