IV型高甘油三酯血症患者的大的载脂蛋白E缺乏极低密度脂蛋白亚组分在体外和体内的脂解作用降低。

Reduced lipolysis of large apo E-poor very-low-density lipoprotein subfractions from type IV hypertriglyceridemic subjects in vitro and in vivo.

作者信息

Evans A J, Wolfe B M, Strong W L, Huff M W

机构信息

Department of Medicine, Robarts Research Institute, University of Western Ontario, London, Canada.

出版信息

Metabolism. 1993 Jan;42(1):105-15. doi: 10.1016/0026-0495(93)90180-v.

DOI:10.1016/0026-0495(93)90180-v

PMID:8446037

Abstract

Heparin-Sepharose chromatography was used to separate Sf 60-400 very-low-density lipoproteins (VLDL) from type IV hypertriglyceridemic subjects into apolipoprotein (apo) E-poor and apo E-rich subfractions. Since we have previously demonstrated that the apo E-poor fraction accumulates in plasma of type IV subjects, the aim of the present studies was to determine whether it was resistant to lipolysis in comparison to the apo E-rich fraction. The apo E-rich fraction was found to be 30% more effective than the apo E-poor fraction at competing with a glycerol tri[1-14C]oleate emulsion for in vitro lipolysis by normolipidemic human post-heparin plasma (P < .01), when assayed under conditions in which both lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL) were active. Similar results were obtained when bovine milk LPL was used as the source of lipolytic activity (P < .025 for apo E-rich relative to apo E-poor VLDL), while neither fraction competed effectively with the synthetic substrate for lipolysis by HTGL only. When equal amounts of triglyceride from VLDL subfractions were incubated with bovine milk LPL, 25% more free fatty acid was released from the apo E-rich fraction than from the apo E-poor fraction (P < .025). The effects of heparin-induced lipolysis in vivo in type IV subjects on the relative amounts and composition of these VLDL subfractions were also assessed. Heparin infusion was associated with a 50% reduction in plasma Sf 60-400 VLDL triglyceride concentration. In addition, heparin-induced lipolysis resulted in a marked decrease in the relative amount of apo E-rich VLDL, while the relative amount of apo E-poor VLDL was increased. These results demonstrate that the apo E-poor VLDL subfraction is resistant to lipolysis by LPL relative to its apo E-rich counterpart, suggesting that reduced lipolytic efficiency may contribute to its observed accumulation in plasma of type IV subjects.

摘要

采用肝素-琼脂糖层析法，将IV型高甘油三酯血症患者的Sf 60 - 400极低密度脂蛋白（VLDL）分离为载脂蛋白（apo）E含量低和apo E含量高的亚组分。由于我们之前已证明IV型患者血浆中apo E含量低的组分有所蓄积，因此本研究的目的是确定与apo E含量高的组分相比，它是否对脂解有抗性。结果发现，在脂蛋白脂肪酶（LPL）和肝甘油三酯脂肪酶（HTGL）均有活性的条件下进行检测时，与甘油三[1 - 14C]油酸酯乳剂竞争正常血脂的人肝素后血浆的体外脂解作用时，apo E含量高的组分比apo E含量低的组分有效30%（P <.01）。当使用牛乳LPL作为脂解活性来源时，也得到了类似结果（相对于apo E含量低的VLDL，apo E含量高的VLDL的P <.025），而这两个组分都不能有效地与合成底物竞争仅由HTGL进行的脂解作用。当将等量来自VLDL亚组分的甘油三酯与牛乳LPL一起温育时，apo E含量高的组分释放的游离脂肪酸比apo E含量低的组分多25%（P <.025）。还评估了IV型患者体内肝素诱导的脂解作用对这些VLDL亚组分的相对含量和组成的影响。肝素输注使血浆Sf 60 - 400 VLDL甘油三酯浓度降低了50%。此外，肝素诱导的脂解作用导致apo E含量高的VLDL相对含量显著降低，而apo E含量低的VLDL相对含量增加。这些结果表明，相对于apo E含量高的对应物，apo E含量低的VLDL亚组分对LPL介导的脂解有抗性，提示脂解效率降低可能是其在IV型患者血浆中蓄积的原因。