APOLIPOPROTEIN-B METABOLISM IN SUBJECTS WITH DEFICIENCY OF APOLIPOPROTEINS-CIII AND APOLIPOPROTEIN-A-I - EVIDENCE THAT APOLIPOPROTEIN-CIII INHIBITS CATABOLISM OF TRIGLYCERIDE-RICH LIPOPROTEINS BY LIPOPROTEIN-LIPASE INVIVO
APOLIPOPROTEIN-B METABOLISM IN SUBJECTS WITH DEFICIENCY OF APOLIPOPROTEINS-CIII AND APOLIPOPROTEIN-A-I - EVIDENCE THAT APOLIPOPROTEIN-CIII INHIBITS CATABOLISM OF TRIGLYCERIDE-RICH LIPOPROTEINS BY LIPOPROTEIN-LIPASE INVIVO
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DOI：
10.1172/jci112713
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发表时间：
1986-11-01
影响因子：
15.9
通讯作者：
BROWN, WV
中科院分区：
文献类型：
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作者：
GINSBERG, HN;LE, NA;BROWN, WV
以前的数据表明，载脂蛋白（apo）CIII可以抑制甘油三酯水解脂蛋白脂肪酶（LPL）和载脂蛋白E介导的摄取富含甘油三酯的脂蛋白的肝脏。我们研究了载脂蛋白B代谢的极低密度脂蛋白（VLDL），中密度脂蛋白（IDL），低密度脂蛋白（LDL）在两个姐妹篇与载脂蛋白CIII-载脂蛋白AI缺乏症。受试者的VLDL甘油三酯水平降低，LDL胆固醇水平正常，高密度脂蛋白（HDL）胆固醇几乎不存在。注射125 I-VLDL和131 I-LDL后apo B代谢动力学的房室分析显示VLDL apo B的部分分解代谢速率（FCR）比正常快6 - 7倍。同时注射[~ 3 H]甘油可快速催化VLDL甘油三酯。VLDL apo B可快速有效地转化为IDL和LDL。LDL apo B的FCR正常。体外实验表明，虽然血清载脂蛋白CIII-载脂蛋白AI缺乏模式能够正常激活纯化的LPL，这些血清的体积增加并没有导致LPL活性的进行性抑制与正常血清证明。将纯化的载脂蛋白CIII添加到缺陷血清中，与用相同体积的天然缺陷血清获得的活性水平相比，导致最大LPL活性降低20-50%。这些体外研究以及体内结果表明，在正常受试者中，载脂蛋白C III可抑制脂蛋白酶脂肪酶对富含甘油三酯的脂蛋白的催化作用。
Previous data suggest that apolipoprotein(apo) CIII may inhibit both triglyceride hydrolyisis by lipoprotein lipase (LPL) and apo E-mediated uptake of triglyceride-rich lipoproteins by the liver. We studied apo B metabolism in very low density (VLDL), intermediate density (IDL), and low density lipoproteins (LDL) in two sisters with apo CIII-apo AI deficiency. The subjects had reduced levels of VLDL triglyceride, normal LDL cholesterol, and near absence of high density lipoprotein (HDL) cholesterol. Compartmental analysis of the kinetics of apo B metabolism after injection of 125I-VLDL and 131I-LDL revealed fractional catabolic rates (FCR) for VLDL apo B that were six to seven times faster than normal. Simultaneous injection of [3H]glycerol demonstrated rapid catabolism of VLDL triglyceride. VLDL apo B was rapidly and efficiently converted to IDL and LDL. The FCR for LDL apo B was normal. In vitro experiments indicated that, although sera from the apo CIII-apo-AI deficient patterns were able to normally activate purified LPL, increasing volumes of these sera did not result in the progressive inhibition of LPL activity demonstrable with normal sera. Addition of purified apo CIII to the deficient sera resulted in 20-50% reductions in maximal LPL activity compared with levels of activity attained with the same volumes of the native, deficient sera. These in vitro studies, together with the in vivo results, indicate that in normal subjects apo CIII can inhibit the catabolism of triglyceride-rich lipoproteins by lipoproteinase lipase.