A rote of LPL n obesity-A study using LPL transgenic rabbits

LPL与肥胖的关系——利用LPL转基因兔进行的研究

• 批准号: 14570150
• 负责人: MORIMOTO Masatoshi
• 金额: $ 2.11万
• 依托单位: Saga University (2004)佐賀医科大学 (2002-2003)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14570150/
• 关键词: Obesity; lipoprotein lipase; Insulin resistant; Transgenic; Rabbit; 遺伝子組換えウサギ; トランスジェニックウサギ

In this study, we examined a rote of lipoprotein lipase(LPL) in the obesity using LPL transgenic rabbits generated by our laboratory. Under normal diet, LPL activity in transgenic rabbit was increased 3-5 times and plasma triglyceride(TG) level in mate transgenic rabbit was decreased to 1/5 compared to control rabbits. In addition, total cholesterol(TC), high density lipoprotein(HDL), free fatty acid(FFA) decreased significantly in LPL transgenic rabbits. Further experiment, LPL transgenic rabbit was fed a 10% high-fat diet to induce obese condition and examined a change of lipoprotein profile. The significant difference was not found in weight gain after feeding of high-fat diet between LPL transgenic and control rabbits, but the transgenic rabbit showed a tendency to have a light body weight. MRI analysis revealed that fat accumulation in LPL transgenic rabbit was smaller than that in control rabbit Actually, fat weight in LPL transgenic rabbit was significantly lower. After feeding of high-fat diet, plasma glucose and insulin levels in control rabbit were significantly increased, but those levels in LPL transgenic rabbit were not different from initial value at start of experiment. In glucose tolerance test, the area under the curve(AUC) of glucose, insulin and FFA in LPL transgenic rabbits were significantly lower than that in control rabbits. A Pathological examination revealed that LPL transgenic rabbit has small adipocytes in size and fatty liver according to the deposition of TG. These observations in our study using LPL transgenic rabbits suggested that LPL may inhibit accumulation of fat and improve insulin sensitivity in obesity induced by high-fat diet feeding.

在这项研究中，我们检测了脂蛋白脂肪酶（LPL）在肥胖中的作用，使用的是我们实验室生产的LPL转基因家兔。正常饲粮条件下，转基因家兔LPL活性较对照组提高3 ~ 5倍，血浆甘油三酯（TG）水平降至对照组的1/5。此外，LPL转基因家兔的总胆固醇（TC）、高密度脂蛋白（HDL）、游离脂肪酸（FFA）均显著降低。实验采用10%高脂饲料诱导LPL转基因家兔肥胖，观察其脂蛋白谱变化。饲喂高脂日粮后，LPL转基因家兔与对照家兔的增重无显著差异，但转基因家兔的体重有偏轻的趋势。MRI分析显示，LPL转基因家兔的脂肪积累量比对照组小，脂肪质量明显降低。饲喂高脂日粮后，对照组血糖和胰岛素水平显著升高，而LPL转基因家兔血糖和胰岛素水平与试验开始时无显著差异。糖耐量试验中，LPL转基因家兔的葡萄糖、胰岛素和FFA曲线下面积（AUC）均显著低于对照组。病理检查显示LPL转基因家兔脂肪细胞体积小，TG沉积呈脂肪肝。我们对LPL转基因家兔的研究表明，LPL可以抑制脂肪的积累，改善高脂肪饮食引起的肥胖的胰岛素敏感性。

项目成果

ヒト疾患モデルとしてのトランスジェニックウサギの開発,繁殖・維持ならびに精子・胚の凍結保存

人类疾病模型转基因兔的开发、培育和维持，以及精子和胚胎的冷冻保存

• 发表时间: 2003
• 期刊: アニテックス 15
• 作者: 北嶋修司

Analysis of intervention to insulin resistance of lipoprotein lipase using WHHL transgenic rabbit

WHHL转基因兔对脂蛋白脂肪酶胰岛素抵抗的干预分析

• 发表时间: 2003
• 期刊: Diabetes Frontier. 14
• 作者: Fan J;Koike T;Liang J;Wang X;Ichikawa T;Kitajima S;Morimoto M;Watanabe T.
• 通讯作者: Watanabe T.

Transgenic Rabbits : Production and Application for Human Disease Models.

转基因兔：人类疾病模型的生产和应用。

• 发表时间: 2003
• 期刊: Recent Res. Devel. Biophys. Biochem. 3
• 作者: Kitajima;S. et al.
• 通讯作者: S. et al.

High lipoprotein lipase activity increases insulin sensitivity in transgenic rabbits

• DOI: 10.1016/j.metabol.2004.07.021
• 发表时间: 2005-01-01
• 期刊: METABOLISM-CLINICAL AND EXPERIMENTAL
• 影响因子: 9.8
• 作者: Liu, EQ;Kitajima, S;Fan, JL
• 通讯作者: Fan, JL

Overexpression of lipoprotein lipase in transgenic rabbits leads to increased small dense LDL in plasma and promotes atherosclerosis

• DOI: 10.1038/labinvest.3700102
• 发表时间: 2004-06-01
• 期刊: LABORATORY INVESTIGATION
• 影响因子: 5
• 作者: Ichikawa, T;Kitajima, S;Fan, JL
• 通讯作者: Fan, JL