Delayed clearance of chylomicron remnants following vitamin-A-containing oral fat loads in broad-beta disease (type III hyperlipoproteinemia).
Delayed clearance of chylomicron remnants following vitamin-A-containing oral fat loads in broad-beta disease (type III hyperlipoproteinemia).
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广泛β病（III型高脂蛋白血症）中含维生素A的口腔脂肪负荷后乳糜微粒残留物的清除延迟。
DOI：
10.1016/0026-0495(76)90149-9
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发表时间：
1976
期刊：
影响因子：
--
通讯作者：
Edwin L. Bierman
中科院分区：
文献类型：
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作者：
William R. Hazzard;William R. Hazzard;Edwin L. Bierman;Edwin L. Bierman
乳糜微粒“残余物”是通过脂蛋白脂肪酶催化的甘油三酯的选择性去除而形成的。为了研究宽β疾病（III型高脂蛋白血症）病理生理学中这些残留物清除的可能缺陷，患有该疾病的受试者和具有内源性高脂蛋白血症（和IV型脂蛋白模式）的对照受试者口服含100 mg视黄酯的脂肪负荷（玉米油：可可脂，1：1，50 g/sqM），含或不含15 μCi 15- 14 C-视黄醇（43.7 mCi/mg）。依次测定乳糜微粒（Sf> 400）和极低密度脂蛋白中甘油三酯和维生素A的含量选择维生素A作为外源性甾醇同化的标志物，因为与胆固醇一样，维生素A在小肠中被吸收，并在乳糜微粒核心中以酯化形式与甘油三酯共分泌;然而，与胆固醇不同的是，一旦胆固醇被肝脏去除，它就不能再循环成VLDL，而只能作为与高密度视黄醇结合蛋白的复合物循环。这些研究证实了乳糜微粒中外源性维生素A的初始浓度，但无一例外地揭示了摄入后24小时VLDL中剩余的Sf> 20维生素A的比例增加。维生素A/甘油三酯的比例也总是增加6和24小时之间的SF 20 -30的亚组分，反映了形成的富含维生素A的“残余物”作为中间物种的乳糜微粒和极低密度脂蛋白的caterectin。在轻度至中度内源性高甘油三酯血症的患者中，Sf> 400的维生素A/甘油三酯比率在6至24小时之间下降，反映了维生素A通过该部分的有效通道和/或富含甘油三酯的Sf> 400颗粒的持续分泌。在严重内源性高甘油三酯血症的患者中，Sf> 400的维生素A/甘油三酯比值的峰值和下降均延迟。然而，在宽β疾病患者中，所有VLDL亚组分的维生素A/甘油三酯比值在6 - 24小时之间增加是常见的，并且在Sf> 400的脂蛋白中不变，无论先前的高甘油三酯血症的程度如何。尽管其他实验揭示了当这些受试者的基础甘油三酯水平高时，维生素A和甘油三酯同化的类似延迟，甘油三酯水平的显著降低并不能纠正6 - 24小时之间Sf> 400维生素A/甘油三酯比值的升高。采用制备电泳的实验证实了含有高维生素A/甘油三酯比值的VLDL与β-结果表明：（1）VLDL中外源性脂质的转运与VLDL中外源性脂质的转运密切相关，VLDL中外源性脂质的转运与VLDL中外源性脂质的转运密切相关，VLDL中外源性脂质的转运与VLDL中外源性脂质的转运密切相关（2）在高维生素血症患者中，富含维生素A的残余物作为乳糜微粒催化剂的中间产物形成;提示（3）乳糜微粒（和外源性VLDL）残留物可能由于清除缺陷而在宽β疾病受试者的血浆中蓄积，和/或或可能对该病症特异的其他卡他霉素。
Chylomicron “remnants” are formed by the selective removal of triglyceride catalyzed by lipoprotein lipase. To investigate a possible defect in the clearance of these remnants in the pathophysiology of broad-β disease (type III hyperlipoproteinemia), subjects with this disorder and comparison subjects with endogenous hypertriglyceridemia (and type IV lipoprotein patterns) ingested an oral fat load (corn oil:cocoa butter, 1:1, 50 g/sqM) containing retinyl ester, 100 mg, with or without 15 μCi 15-14C-retinol (43.7 mCi/mg). The content of triglyceride and vitamin A was sequentially determined in chylomicrons (Sf> 400) and very low density lipoproteins (VLDL, Sf20–400) over the ensuing 24–72 hr. Vitamin A was chosen as a marker for exogenous sterol assimilation since, like cholesterol, it is absorbed in the small intestine and cosecreted in esterified form with triglyceride in the chylomicron core; however, unlike cholesterol, once having been removed by the liver, it cannot be recycled into VLDL, but subsequently circulates only as a complex with the high density retinol binding protein. Thus measurements of the vitamin A/triglyceride ratio in Sf> 20 lipoproteins reflected the relative efficiency of vitamin A versus triglyceride removal within these lipoproteins.These studies confirmed the initial concentration of exogenous vitamin A in chylomicrons but invariably disclosed an increasing proportion of the remaining Sf> 20 vitamin A in VLDL 24 hr after its ingestion. The vitamin A/triglyceride ratio also invariably increased between 6 and 24 hr in the Sf20–30 subfraction, reflecting the formation of vitamin A-rich “remnants” as intermediate species in the catabolism of chylomicrons and VLDL. Among those with mild to moderate endogenous hypertriglyceridemia the Sf> 400 vitamin A/triglyceride ratio declined between 6 and 24 hr, reflecting the efficient passage of the vitamin A through this fraction and/or continued secretion of Sf> 400 particles rich in triglyceride. Among those with severe endogenous hypertriglyceridemia, both the peak and decline in the Sf> 400 vitamin A/triglyceride ratio were delayed. However, among those with broad-β disease, an increasing vitamin A/triglyceride ratio between 6 and 24 hr was frequent within all VLDL subfractions and invariable among lipoproteins of Sf> 400 regardless of the degree of antecedent hypertriglyceridemia. Although additional experiments disclosed a similar delay in both vitamin A and triglyceride assimilation when basal triglyceride levels were high in these subjects, marked reduction of triglyceride levels did not correct the rise in the Sf> 400 vitamin A/triglyceride ratio between 6 and 24 hr. Experiments employing preparative electrophoresis confirmed the identity of VLDL containing a high vitamin A/triglyceride ratio with the β-VLDL which accumulate in broad-β disease.Thus these studies demonstrate: (1) the transport of exogenous lipid in VLDL (usually presumed to be entirely of endogenous origin); (2) the formation of vitamin A-rich remnants as intermediates in chylomicron catabolism in hypertriglyceridemic subjects; and suggest that (3) chylomicron (and exogenously-derived VLDL) remnants may accumulate in the plasma of subjects with broad-β disease by virtue of a defect in their removal and/or further catabolism which may be specific to this disorder.