Hypertriglyceridemia and delayed clearance of fat load in transgenic rabbits expressing human apolipoprotein CIII
Hypertriglyceridemia and delayed clearance of fat load in transgenic rabbits expressing human apolipoprotein CIII
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DOI：
10.1007/s11248-010-9467-5
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发表时间：
2011-08-01
影响因子：
3
通讯作者：
Liu, Enqi
中科院分区：
文献类型：
--
作者：
Ding, Yinyuan;Wang, Yuhui;Liu, Enqi
载脂蛋白CIII （apoCIII）与高甘油三酯血症有关，血浆apoCIII独立预测冠心病的风险。虽然高甘油三酯血症患者已被证明与血浆apoCIII水平升高和脂蛋白脂肪酶（LPL）活性降低相关，但apoCIII转基因小鼠显示LPL活性升高。在本研究中，我们在肝脏中产生了完全表达人apoCIII基因的转基因（Tg）家兔，并研究了apoCIII过表达对家兔脂质代谢的影响。与非Tg组相比，Tg组饲粮和空腹血浆甘油三酯分别增加3倍和3.2倍。Tg组和非Tg组血浆总胆固醇和高密度脂蛋白胆固醇水平无显著差异。脂蛋白组分分析显示Tg家兔血浆甘油三酯水平升高主要是由于极低密度脂蛋白/乳糜微粒的增加。此外，与非Tg对照组相比，Tg家兔的血浆甘油三酯清除明显延迟，肝素后血浆LPL活性显著降低。总之，这些结果表明apoCIII转基因家兔通过延迟清除血浆甘油三酯而发生高甘油三酯血症的机制与高甘油三酯血症患者相似，可以作为研究人类高脂血症与动脉粥样硬化疾病关系的有价值的工具。
Apolipoprotein CIII (apoCIII) has been implicated in hypertriglyceridemia and plasma apoCIII independently predicts risk for coronary heart disease. While hypertriglyceridemia in patients has been demonstrated to correlate with elevated plasma apoCIII levels and reduced lipoprotein lipase (LPL) activity, apoCIII transgenic mice show elevated LPL activity. In this study, we generated transgenic (Tg) rabbits expressing human apoCIII gene exclusively in liver and investigated the effect of apoCIII overexpression on lipid metabolism of rabbits. In comparison with non-Tg littermates, Tg rabbits had 3- and 3.2-fold increases in fed and fasted plasma triglycerides, respectively. In contrast, no significant differences were observed in plasma total cholesterol and high density lipoprotein cholesterol levels between Tg and non-Tg rabbits. Analysis of lipoprotein fractions revealed that elevated plasma triglyceride levels in Tg rabbits were mainly attributed to an increase in very low density lipoprotein/chylomicron-sized particles. Furthermore, Tg rabbits showed markedly delayed clearance of plasma triglycerides accompanied with significantly reduced LPL activity in post-heparin plasma compared to that in non-Tg controls. In conclusion, these results indicate apoCIII transgenic rabbits develop hypertriglyceridemia with similar mechanism in hypertriglyceridemic patients via delayed clearance of plasma triglycerides, and could be used as a valuable tool for the study of human hyperlipidemia in relation with atherosclerotic disorders.