Hazzard W R, Bierman E L
Metabolism. 1976 Jul;25(7):777-801. doi: 10.1016/0026-0495(76)90149-9.
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-beta 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/sq M) containing retinyl ester, 100 mg, with or without 15 muCi 15-(14) C-retinol (43.7 mCi/mg). The content of triglyceride and vitamin A was sequentially determined in chylomicrons (Sf more than 400) and very low density lipoproteins (VLDS, 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 inot 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 greater than 20 lipoproteins reflected the relative efficiency of vitamin A versus triglyceride removal within these lipoproteins. These studies confirmed the intital concentration of exogenous vitamin A in chylomicrons but invariably disclosed an increasing proportion of the remaining Sf greater than 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 greater than 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 greater than 400 particles rich in triglyceride. Among those with severe endogenous hypertriglyceridemia, both the peak and decline in the Sf greater than 400 vitamin A/triglyceride ratio were delayed. However, among those with broad-beta disease, an increasing vitamin A/triglyceride ratio between 6 and 24 hr was frequent within all VLDL subfractions and invariable among lipoproteins of Sf greater than 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 greater than 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 beta-VLDL which accumulate in broad-beta disease...
乳糜微粒“残粒”是由脂蛋白脂肪酶催化的甘油三酯选择性去除而形成的。为了研究在宽β病（III型高脂蛋白血症）的病理生理学中这些残粒清除可能存在的缺陷，患有这种疾病的受试者以及患有内源性高甘油三酯血症（和IV型脂蛋白模式）的对照受试者摄入了含有100毫克视黄酯的口服脂肪负荷（玉米油：可可脂，1:1，50克/平方米），有或没有15微居里15-(14)C-视黄醇（43.7毫居里/毫克）。在随后的24至72小时内，依次测定乳糜微粒（Sf大于400）和极低密度脂蛋白（VLDL，Sf20 - 400）中甘油三酯和维生素A的含量。选择维生素A作为外源性固醇同化的标志物，因为它与胆固醇一样，在小肠中被吸收，并以酯化形式与乳糜微粒核心中的甘油三酯共分泌；然而，与胆固醇不同，一旦被肝脏清除，它就不能再循环到VLDL中，而是随后仅作为与高密度视黄醇结合蛋白的复合物循环。因此，对Sf大于20的脂蛋白中维生素A/甘油三酯比值进行测量，反映了这些脂蛋白中维生素A相对于甘油三酯清除的相对效率。这些研究证实了乳糜微粒中外源性维生素A的初始浓度，但在摄入后24小时，始终发现剩余的Sf大于20的维生素A在VLDL中的比例增加。在Sf20 - 30亚组分中，维生素A/甘油三酯比值在6至24小时之间也始终增加，反映出富含维生素A的“残粒”作为乳糜微粒和VLDL分解代谢中的中间产物形成。在轻度至中度内源性高甘油三酯血症患者中，Sf大于400的维生素A/甘油三酯比值在6至24小时之间下降，反映出维生素A有效通过该组分和/或持续分泌富含甘油三酯的Sf大于400颗粒。在重度内源性高甘油三酯血症患者中，Sf大于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病患者中，在所有VLDL亚组分中，6至24小时之间维生素A/甘油三酯比值增加很常见，并且在Sf大于400的脂蛋白中无论先前高甘油三酯血症的程度如何都是不变的。尽管额外的实验表明，当这些受试者的基础甘油三酯水平较高时，维生素A和甘油三酯的同化都有类似的延迟，但甘油三酯水平的显著降低并不能纠正6至24小时之间Sf大于400的维生素A/甘油三酯比值的升高。采用制备电泳的实验证实了宽β病中积累的β-VLDL与含有高维生素A/甘油三酯比值的VLDL具有同一性……
