Department of Clinical Pathology, Lipid Laboratory and Center for Medicine and Experimental Surgery, Faculty of Medical Sciences, University of Campinas, Rua Tessália Vieira de Camargo, Campinas 13084-971, Brazil.
Lipids Health Dis. 2011 May 24;10:87. doi: 10.1186/1476-511X-10-87.
The relationship between CETP and postprandial hyperlipemia is still unclear. We verified the effects of varying activities of plasma CETP on postprandial lipemia and precocious atherosclerosis in asymptomatic adult women.
Twenty-eight women, selected from a healthy population sample (n = 148) were classified according to three CETP levels, all statistically different: CETP deficiency (CETPd ≤ 4.5%, n = 8), high activity (CETPi ≥ 23.8, n = 6) and controls (CTL, CETP ≥ 4.6% and ≤ 23.7%, n = 14). After a 12 h fast they underwent an oral fat tolerance test (40 g of fat/m² of body surface area) for 8 hours. TG, TG-rich-lipoproteins (TRL), cholesterol and TRL-TG measurements (AUC, AUIC, AR, RR and late peaks) and comparisons were performed on all time points. Lipases and phospholipids transfer protein (PLTP) were determined. Correlation between carotid atherosclerosis (c-IMT) and postprandial parameters was determined. CETP TaqIB and I405V and ApoE-ε3/ε2/ε4 polymorphisms were examined. To elucidate the regulation of increased lipemia in CETPd a multiple linear regression analysis was performed.
In the CETPi and CTL groups, CETP activity was respectively 9 and 5.3 higher compared to the CETPd group. Concentrations of all HDL fractions and ApoA-I were higher in the CETPd group and clearance was delayed, as demonstrated by modified lipemia parameters (AUC, AUIC, RR, AR and late peaks and meal response patterns). LPL or HL deficiencies were not observed. No genetic determinants of CETP deficiency or of postprandial lipemia were found. Correlations with c-IMT in the CETPd group indicated postprandial pro-atherogenic associations. In CETPd the regression multivariate analysis (model A) showed that CETP was largely and negatively predicted by VLDL-C lipemia (R² = 92%) and much less by TG, LDL-C, ApoAI, phospholipids and non-HDL-C. CETP (model B) influenced mainly the increment in ApoB-100 containing lipoproteins (R² = 85% negatively) and phospholipids (R² = 13%), at the 6(th)h point.
The moderate CETP deficiency phenotype included a paradoxically high HDL-C and its sub fractions (as earlier described), positive associations with c-IMT, a postprandial VLDL-C increment predicting negatively CETP activity and CETP activity regulating inversely the increment in ApoB100-containing lipoproteins. We hypothesize that the enrichment of TG content in triglyceride-rich ApoB-containing lipoproteins and in TG rich remnants increases lipoproteins' competition to active lipolysis sites,reducing their catabolism and resulting on postprandial lipemia with atherogenic consequences.
CETP 与餐后高脂血症的关系仍不清楚。我们验证了血浆 CETP 活性的变化对无症状成年女性餐后血脂和早发动脉粥样硬化的影响。
从健康人群样本（n=148）中选择 28 名女性，根据三种 CETP 水平进行分类：CETP 缺乏（CETPd ≤ 4.5%，n=8）、高活性（CETPi ≥ 23.8，n=6）和对照组（CTL，CETP ≥ 4.6%和≤23.7%，n=14）。禁食 12 小时后，她们接受了 40 克脂肪/平方米体表面积的口服脂肪耐量试验（8 小时）。在所有时间点都进行了 TG、富含 TG 的脂蛋白（TRL）、胆固醇和 TRL-TG 测量（AUC、AUIC、AR、RR 和晚期峰值）和比较。还测定了脂肪酶和磷脂转移蛋白（PLTP）。确定颈动脉粥样硬化（c-IMT）与餐后参数的相关性。还检查了 CETP TaqIB 和 I405V 以及 ApoE-ε3/ε2/ε4 多态性。为了阐明 CETPd 中脂血症增加的调节作用，进行了多元线性回归分析。
在 CETPi 和 CTL 组中，CETP 活性分别比 CETPd 组高 9 倍和 5.3 倍。CETPd 组所有 HDL 亚组分和 ApoA-I 的浓度均较高，清除延迟，如改良脂血症参数（AUC、AUIC、RR、AR 和晚期峰值和膳食反应模式）所示。未观察到 LPL 或 HL 缺乏。未发现 CETP 缺乏或餐后脂血症的遗传决定因素。在 CETPd 组与 c-IMT 的相关性表明，餐后存在促动脉粥样硬化的关联。在 CETPd 中，多元回归分析（模型 A）表明，VLDL-C 脂血症（R²=92%）在很大程度上负预测 CETP，而 TG、LDL-C、ApoAI、磷脂和非 HDL-C 的预测作用较小。CETP（模型 B）主要影响载脂蛋白 B-100 含量增加的脂蛋白（R²=-85%）和磷脂（R²=13%），在第 6 小时。
中等程度的 CETP 缺乏表型包括矛盾的高 HDL-C 及其亚组分（如前所述），与 c-IMT 呈正相关，餐后 VLDL-C 增加与 CETP 活性呈负相关，而 CETP 活性与载脂蛋白 B100 含量增加的脂蛋白呈负相关。我们假设富含 TG 的甘油三酯富含载脂蛋白 B 的脂蛋白和富含 TG 的残基中的 TG 含量增加，增加了脂蛋白对活性脂肪酶部位的竞争，减少了它们的代谢，导致餐后脂血症，并产生促动脉粥样硬化的后果。
