Liu M S, Jirik F R, LeBoeuf R C, Henderson H, Castellani L W, Lusis A J, Ma Y, Forsythe I J, Zhang H, Kirk E
Department of Medical Genetics, University of British Columbia, Vancouver, Canada.
J Biol Chem. 1994 Apr 15;269(15):11417-24.
Lipoprotein lipase (LPL) is a key enzyme required for the hydrolysis of triglyceride-rich particles. To assess the effects of increased plasma LPL on lipoprotein levels, transgenic mice expressing human LPL (hLPL) were produced. Abundant hLPL transcripts were detected in RNA from different tissues of transgenic mice which resulted in an increase in post-heparin plasma LPL activity of approximately 154%. On rodent chow (p = 0.01) and after a 16-h fast (p = 0.001), plasma triglycerides in transgenic mice were decreased by approximately 50% as compared to littermate controls. Gel filtration chromatography showed a 2-3-fold decrease in very low density lipoprotein triglycerides and cholesterol enrichment of low density lipoprotein. Transgenic mice maintained on a high carbohydrate diet exhibited a 78% (p = 0.03) lowering of low density lipoprotein and very low density lipoprotein cholesterol levels, in addition to a 68% (p = 0.01) lowering of total to high density lipoprotein cholesterol (TC/HDL-C) ratios compared to controls. The distribution of apoA-I and A-II were similar in the transgenics and their non-transgenic littermates, while the apoE distribution was mildly altered in the plasma from the transgenic mice. These data demonstrate that moderate increases in total LPL activity are associated with significant changes in lipoprotein levels and altered composition of lipoprotein particles.
脂蛋白脂肪酶（LPL）是富含甘油三酯颗粒水解所需的关键酶。为了评估血浆LPL增加对脂蛋白水平的影响，制备了表达人LPL（hLPL）的转基因小鼠。在转基因小鼠不同组织的RNA中检测到丰富的hLPL转录本，这导致肝素后血浆LPL活性增加约154%。与同窝对照相比，在啮齿动物饲料喂养时（p = 0.01）以及禁食16小时后（p = 0.001），转基因小鼠的血浆甘油三酯降低了约50%。凝胶过滤色谱显示极低密度脂蛋白甘油三酯减少2 - 3倍，低密度脂蛋白胆固醇富集。与对照组相比，维持高碳水化合物饮食的转基因小鼠的低密度脂蛋白和极低密度脂蛋白胆固醇水平降低了78%（p = 0.03），总胆固醇与高密度脂蛋白胆固醇（TC/HDL-C）比值降低了68%（p = 0.01）。转基因小鼠及其非转基因同窝小鼠中载脂蛋白A-I和A-II的分布相似，而转基因小鼠血浆中载脂蛋白E的分布略有改变。这些数据表明，LPL总活性的适度增加与脂蛋白水平的显著变化以及脂蛋白颗粒组成的改变有关。
