Overexpression of lipoprotein lipase in transgenic watanabe heritable hyperlipidemic rabbits improves hyperlipidemia and obesity
Overexpression of lipoprotein lipase in transgenic watanabe heritable hyperlipidemic rabbits improves hyperlipidemia and obesity
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DOI：
10.1074/jbc.m311514200
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发表时间：
2004-02-27
影响因子：
4.8
通讯作者：
Fan, JL
中科院分区：
文献类型：
--
作者：
Koike, T;Liang, JY;Fan, JL
脂蛋白脂肪酶（Lipoprotein lipase， LPL）是富含甘油三酯的脂蛋白水解的限速酶，在脂蛋白和游离脂肪酸代谢中起着关键作用。LPL的基因操作可能对治疗高甘油三酯血症有益，但目前尚不清楚LPL活性的增加是否能有效降低家族性高胆固醇血症患者的血浆胆固醇和改善胰岛素抵抗。为了验证刺激LPL表达可以作为治疗纯合子家族性高胆固醇血症的辅助疗法的假设，我们培育了转基因（Tg） Watanabe遗传性高脂血症（WHHL）兔子，这些兔子过度表达人类LPL转基因，并将它们的血浆脂质水平、葡萄糖代谢和体脂肪积累与非Tg WHHL兔子进行比较。过表达LPL可显著改善Tg WHHL兔的高甘油三酯血症。此外，雄性Tg WHHL兔LPL活性的增加也纠正了高胆固醇血症(非Tg组为544+/-52，Tg组为227+/-29 mg/dl， p
Lipoprotein lipase (LPL) is the rate-limiting enzyme for the hydrolysis of the triglyceride-rich lipoproteins and plays a critical role in lipoprotein and free fatty acid metabolism. Genetic manipulation of LPL may be beneficial in the treatment of hypertriglyceridemias, but it is unknown whether increased LPL activity may be effective in lowering plasma cholesterol and improving insulin resistance in familial hypercholesterolemic patients. To test the hypothesis that stimulation of LPL expression may be used as an adjunctive therapy for treatment of homozygous familial hypercholesterolemia, we have generated transgenic (Tg) Watanabe heritable hyperlipidemic (WHHL) rabbits that overexpress the human LPL transgene and compared their plasma lipid levels, glucose metabolism, and body fat accumulation with those of non-Tg WHHL rabbits. Overexpression of LPL dramatically ameliorated hypertriglyceridemia in Tg WHHL rabbits. Furthermore, increased LPL activity in male Tg WHHL rabbits also corrected hypercholesterolemia (544+/-52 in non-Tg versus 227+/-29 mg/dl in Tg, p