Rashid S, Uffelman K D, Barrett P H, Vicini P, Adeli K, Lewis G F
Department of Medicine, Division of Endocrinology, University of Toronto, Toronto, Ontario, Canada M5G 2C4.
J Lipid Res. 2001 Feb;42(2):265-71.
Triglyceride (TG) enrichment of high density lipoprotein (HDL), which occurs in hypertriglyceridemic states, significantly enhances the rate at which HDL apolipoprotein (apo)A-I is cleared from the circulation of healthy humans. In the New Zealand White (NZW) rabbit, a species naturally deficient in hepatic lipase (HL), TG enrichment of HDL requires prior lipolytic modification to enhance apoA-I clearance. However, the effect of TG enrichment of HDL on the subsequent clearance of HDL cholesteryl ester (CE) has not previously been examined in vivo. Therefore, we investigated, in the NZW rabbit, the effect of ex vivo TG enrichment of rabbit HDL (by incubation with human very low density lipoprotein) on the clearance of HDL CE and apoA-I radiolabeled with (3)H-cholesteryl oleyl ether and with (131)I, respectively. In nine experiments, TG enrichment of rabbit HDL resulted in an 87% average increase in HDL TG and a corresponding 31% reduction in HDL CE content. The calculated apoA-I and CE fractional catabolic rates associated with TG-rich versus fasting HDL tracers were not significantly different (apoA-I: 0.119 +/- 0.017 vs. 0.107 +/- 0.024 pools per h, P = 0.68; CE: 0.147 +/- 0.014 vs. 0.114 +/- 0.019 pools per h, P = 0.20). In an animal model deficient in HL, TG enrichment of HDL did not alter the rates of HDL apoA-I or selective CE clearance. Further studies are needed to determine whether, in the presence of HL, TG enrichment of HDL alters selective HDL CE clearance.
在高甘油三酯血症状态下发生的高密度脂蛋白(HDL)甘油三酯(TG)富集,显著提高了HDL载脂蛋白(apo)A-I从健康人体循环中清除的速率。在新西兰白兔(NZW)中,这是一种天然缺乏肝脂酶(HL)的物种,HDL的TG富集需要事先进行脂解修饰以增强apoA-I的清除。然而,HDL的TG富集对随后HDL胆固醇酯(CE)清除的影响此前尚未在体内进行研究。因此,我们在NZW兔中研究了兔HDL的体外TG富集(通过与人极低密度脂蛋白孵育)对分别用(3)H-胆固醇油醚和(131)I放射性标记的HDL CE和apoA-I清除的影响。在9个实验中,兔HDL的TG富集导致HDL TG平均增加87%,同时HDL CE含量相应降低31%。与富含TG的HDL示踪剂和空腹HDL示踪剂相关的计算得出的apoA-I和CE分数分解代谢率没有显著差异(apoA-I:每小时0.119±0.017池对0.107±0.024池,P = 0.68;CE:每小时0.147±0.014池对0.114±0.019池,P = 0.20)。在缺乏HL的动物模型中,HDL的TG富集并未改变HDL apoA-I或选择性CE清除率。需要进一步研究以确定在存在HL的情况下,HDL的TG富集是否会改变选择性HDL CE清除。