University of Southern California, Los Angeles, CA.
University of Southern California, Los Angeles, CA.
Metabolism. 2014 May;63(5):727-34. doi: 10.1016/j.metabol.2014.03.001. Epub 2014 Mar 5.
Our objective was to examine the role of hypertriglyceridemia on the capacity of HDL to facilitate ABCA-1 mediated cholesterol efflux in type 2 diabetes (T2DM).
HDL mediated cholesterol efflux through the ABCA-1 transporter was measured using BHK cell lines in samples of 71 participants with T2DM in the presence or absence of high triglyceride levels (TG). Additionally, HDL mediated efflux was measured in 13 diabetic and non-diabetic participants fasting and four hours after a high-fat test challenge.
HDL mediated cholesterol efflux function was increased in participants with T2DM with hypertriglyceridemia when compared to participants with T2DM without hypertriglyceridemia (efflux ratio mean±standard deviation (SD), T2DM+TG: 1.17±0.25 vs. T2DM - TG: 1.03±0.19, p=0.0098). In the fat challenge study, we observed a significant increase in ABCA-1 mediated cholesterol efflux capacity following an ingestion of high-fat test meal by participants in both groups of T2DM (n=6, efflux ratio, mean±SD, pre: 0.86±0.4 vs. post: 1.34±0.6, p=0.01) and non-diabetic participants (n=7, efflux ratio mean±SD pre: 1.24±0.31 vs. post: 1.39±0.42, p=0.04) that was partly explained by the difference in CETP activity (r=0.6, p=0.03).
Our study suggests that high triglyceride levels facilitate ABCA-1 mediated efflux function of HDL in part by activating CETP.
本研究旨在探讨高三酰甘油血症对 2 型糖尿病(T2DM)患者高密度脂蛋白(HDL)通过 ABCA-1 转运体介导胆固醇外排能力的影响。
采用 BHK 细胞系,在存在或不存在高甘油三酯(TG)水平的情况下,检测 71 例 T2DM 患者样本中 HDL 介导的 ABCA-1 转运体介导的胆固醇外排。此外,在 13 例糖尿病和非糖尿病参与者空腹和高脂肪测试挑战后 4 小时,测量 HDL 介导的外排。
与无高三酰甘油血症的 T2DM 患者相比,高三酰甘油血症的 T2DM 患者的 HDL 介导胆固醇外排功能增加(外排率均值±标准差,T2DM+TG:1.17±0.25 比 T2DM-TG:1.03±0.19,p=0.0098)。在脂肪挑战研究中,我们观察到两组 T2DM 患者(n=6,外排率,均值±SD,餐前:0.86±0.4 比餐后:1.34±0.6,p=0.01)和非糖尿病患者(n=7,外排率均值±SD,餐前:1.24±0.31 比餐后:1.39±0.42,p=0.04)在摄入高脂肪测试餐后,ABCA-1 介导的胆固醇外排能力显著增加,这种增加部分可以用 CETP 活性的差异来解释(r=0.6,p=0.03)。
我们的研究表明,高三酰甘油血症通过激活 CETP 部分促进了 HDL 通过 ABCA-1 介导的外排功能。