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

本研究利用本实验室培育的转脂蛋白脂肪酶(LPL)基因兔，检测了肥胖大白兔体内LPL的变化。在正常饲料条件下，转基因兔LPL活性较对照兔提高3~5倍，血浆甘油三酯(TG)水平降低至对照兔的1/5。此外，转LPL基因兔的总胆固醇(TC)、高密度脂蛋白(HDL)、游离脂肪酸(FFA)显著降低。进一步的实验，用10%的高脂饲料喂养转LPL基因的兔，诱导肥胖，并检测脂蛋白的变化。饲喂高脂饲料后，转LPL基因兔与对照兔的增重差异不显著，但转基因兔有体重减轻的趋势。MRI分析表明，转LPL基因兔的脂肪积聚明显小于对照兔，而转LPL基因兔的脂肪重量明显低于对照组。饲喂高脂饲料后，对照组的血糖和胰岛素水平显著升高，而转LPL基因兔的血糖和胰岛素水平与实验开始时无明显差异。在糖耐量试验中，转LPL基因兔的血糖、胰岛素和游离脂肪酸的曲线下面积(AUC)显著低于对照兔。病理检查显示转LPL基因兔脂肪细胞体积较小，甘油三酯沉积形成脂肪肝。本研究用LPL转基因兔进行的研究表明，LPL可抑制高脂饮食诱导的肥胖大鼠的脂肪蓄积，改善胰岛素敏感性。

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.