Apolipoprotein C-III deficiency accelerates triglyceride hydrolysis by lipoprotein lipase in wild-type and apoE knockout mice.
Apolipoprotein C-III deficiency accelerates triglyceride hydrolysis by lipoprotein lipase in wild-type and apoE knockout mice.
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发表时间：
2001-10
影响因子：
6.5
通讯作者：
M. Jong;P. Rensen;V. Dahlmans;H. V. D. Boom;T. J. V. Berkel;L. Havekes
中科院分区：
文献类型：
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作者：
M. Jong;P. Rensen;V. Dahlmans;H. V. D. Boom;T. J. V. Berkel;L. Havekes
以往对高甘油三酯血症APOC3转基因小鼠的研究表明，载脂蛋白C-III(apoC-III)可能抑制载脂蛋白E介导的肝脏对富含甘油三酯的脂蛋白的摄取和/或脂蛋白脂酶(LPL)介导的甘油三酯的水解。因此，APOC3基因敲除(APOC3(-/-))小鼠是低甘油三酯血症的。在本研究中，我们试图通过将载脂蛋白C 3(-/-)小鼠与载脂蛋白E(-/-)小鼠杂交来研究载脂蛋白C-III缺乏在高脂血症背景下的影响，以阐明这些现象背后的机制(S)。与apoE(+/+)apoC3(-/-)小鼠相似，apoE(-/-)apoC3(-/-)小鼠显著降低极低密度脂蛋白和甘油三酯，表明apoC-III缺乏发挥降脂作用的机制(S)不依赖于apoE。在这两种背景下，APOC3(-/-)小鼠表现出正常的肠道脂肪吸收和肝脏VLDLTG分泌。然而，周转研究表明，在APOC3(-/-)小鼠中，TG标记的乳剂颗粒被清除得更快，而作为肝脏摄取整个颗粒的标志的极低密度脂蛋白apoB的清除不受影响。此外，研究表明，在APOC3(-/-)小鼠中，胆固醇油酸盐标记的颗粒也被更快地清除。因此，APOC3(-/-)小鼠发生低脂血症的机制既涉及更有效的VLDLTG的水解，也涉及增强VLDL胆固醇酯从血浆中的选择性清除。综上所述，我们对APOC3(-/-)小鼠的研究支持apoC-III是极低密度脂蛋白TG水解酶的有效抑制因子的概念，并揭示了apoC-III在胆固醇酯选择性摄取方面的潜在调节作用。
Previous studies with hypertriglyceridemic APOC3 transgenic mice have suggested that apolipoprotein C-III (apoC-III) may inhibit either the apoE-mediated hepatic uptake of TG-rich lipoproteins and/or the lipoprotein lipase (LPL)-mediated hydrolysis of TG. Accordingly, apoC3 knockout (apoC3(-/-)) mice are hypotriglyceridemic. In the present study, we attempted to elucidate the mechanism(s) underlying these phenomena by intercrossing apoC3(-/-) mice with apoE(-/-) mice to study the effects of apoC-III deficiency against a hyperlipidemic background. Similar to apoE(+/+) apoC3(-/-) mice, apoE(-/-)apoC3(-/-) mice exhibited a marked reduction in VLDL cholesterol and TG, indicating that the mechanism(s) by which apoC-III deficiency exerts its lipid-lowering effect act independent of apoE. On both backgrounds, apoC3(-/-) mice showed normal intestinal lipid absorption and hepatic VLDL TG secretion. However, turnover studies showed that TG-labeled emulsion particles were cleared much more rapidly in apoC3(-/-) mice, whereas the clearance of VLDL apoB, as a marker for whole particle uptake by the liver, was not affected. Furthermore, it was shown that cholesteryl oleate-labeled particles were also cleared faster in apoC3(-/-) mice. Thus the mechanisms underlying the hypolipidemia in apoC3(-/-) mice involve both a more efficient hydrolysis of VLDL TG as well as an enhanced selective clearance of VLDL cholesteryl esters from plasma. In summary, our studies of apoC3(-/-) mice support the concept that apoC-III is an effective inhibitor of VLDL TG hydrolysis and reveal a potential regulating role for apoC-III with respect to the selective uptake of cholesteryl esters.