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

本研究采用脂蛋白脂酶（LPL）转基因家兔，检测LPL在肥胖中的作用。在正常饮食条件下，转基因兔的LPL活性比对照兔提高3-5倍，而转基因兔的血浆甘油三酯（TG）水平比对照兔降低1/5。LPL转基因兔血清总胆固醇（TC）、高密度脂蛋白（HDL）、游离脂肪酸（FFA）含量显著降低。进一步的实验，LPL转基因兔被喂食10%高脂饮食以诱导肥胖状态，并检查脂蛋白谱的变化。LPL转基因兔与对照兔在饲喂高脂饲料后的增重差异不显著，但转基因兔表现出体重减轻的趋势。MRI分析显示，LPL转基因兔的脂肪堆积比对照兔小，实际上，LPL转基因兔的脂肪重量显著降低。饲喂高脂饲料后，对照兔的血糖和胰岛素水平显著升高，而LPL转基因兔的血糖和胰岛素水平与实验开始时的初始值无差异。在糖耐量试验中，LPL转基因兔的葡萄糖、胰岛素和游离脂肪酸的曲线下面积（AUC）均显著低于对照兔。病理学检查发现LPL转基因兔脂肪细胞体积小，TG沉积明显，脂肪肝形成。本研究采用LPL转基因兔进行实验，结果表明LPL可以抑制高脂饮食诱导的肥胖动物体内脂肪蓄积，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.