Gylling H, Miettinen T A
Second Department of Medicine, University of Helsinki, Finland.
Atherosclerosis. 1994 Apr;106(2):169-78. doi: 10.1016/0021-9150(94)90122-8.
Serum squalene, a non-steroid intermediate of cholesterol biosynthesis, originates mainly from endogenous cholesterol synthesis and partly from diet, especially in populations consuming a lot of olive oil rich in squalene. Its postabsorptive metabolism has not been studied in detail in humans. Its presence in chylomicrons and VLDL suggests that the removal of dietary squalene may reflect the metabolism of intestinal lipoproteins. Accordingly, we studied the postabsorptive metabolism of 1 g dietary squalene in 16 healthy subjects with apolipoprotein (apo) E 3/3 phenotype and in five type III hyperlipidemic apo E 2/2 homozygotes known to have a retarded chylomicron remnant removal, and compared the results with vitamin A fat load test. About 40% of the basal and 90% of the postabsorptive squalene was in lipoproteins < 1.019 g/ml. The peak concentrations of chylomicron squalene were at 6 h, and of triglyceride-rich nonchylo-fraction at 9-12 h in the controls. The peak values occurred later than those of vitamin A. At 24 h the levels still exceeded the basal ones. In type III dyslipoproteinemia, most of the basal and postabsorptive squalene was in lipoproteins of density less than 1.019 g/ml, the peak postabsorptive values occurred later than in the controls and the serum values remained above the control levels for up to 24 h. The squalene and vitamin A areas under the incremental response curves (AUC) were higher than in the control group. The AUCs of the two markers in chylomicron were correlated negatively and those in LDL+HDL were correlated positively with fasting HDL cholesterol levels, the respective correlations being opposite with fasting VLDL triglycerides. The postabsorptive profile of squalene levels resembled that of vitamin A in both groups, except that the squalene curves were shifted to a later time period. Thus, a delayed clearance of chylomicron remnants could be detected by analyzing serum squalene 6-24 h after the squalene-supplemented fat meal.
血清角鲨烯是胆固醇生物合成的一种非甾体中间体,主要源自内源性胆固醇合成,部分来自饮食,尤其是在大量食用富含角鲨烯的橄榄油的人群中。其吸收后代谢在人体中尚未得到详细研究。它在乳糜微粒和极低密度脂蛋白中的存在表明,膳食角鲨烯的清除可能反映了肠道脂蛋白的代谢。因此,我们研究了16名载脂蛋白(apo)E 3/3表型的健康受试者和5名已知乳糜微粒残粒清除延迟的III型高脂血症apo E 2/2纯合子摄入1g膳食角鲨烯后的吸收后代谢情况,并将结果与维生素A脂肪负荷试验进行比较。基础状态下约40%的角鲨烯以及吸收后90%的角鲨烯存在于密度<1.019g/ml的脂蛋白中。对照组中,乳糜微粒角鲨烯的峰值浓度出现在6小时,富含甘油三酯的非乳糜微粒部分的峰值浓度出现在9至12小时。这些峰值出现的时间比维生素A的峰值晚。在24小时时,其水平仍超过基础水平。在III型血脂异常中,基础状态和吸收后大部分角鲨烯存在于密度小于1.019g/ml的脂蛋白中,吸收后峰值出现的时间比对照组晚,血清值在长达24小时内一直高于对照组水平。角鲨烯和维生素A增量反应曲线下的面积(AUC)高于对照组。乳糜微粒中两种标志物的AUC呈负相关,低密度脂蛋白+高密度脂蛋白中的AUC与空腹高密度脂蛋白胆固醇水平呈正相关,各自的相关性与空腹极低密度脂蛋白甘油三酯的相关性相反。两组中角鲨烯水平的吸收后曲线与维生素A相似,只是角鲨烯曲线向后推迟了一段时间。因此,在补充角鲨烯的脂肪餐后6至24小时分析血清角鲨烯,可以检测到乳糜微粒残粒清除延迟。