Department of Medicine, Baylor College of Medicine, One Baylor Plaza, Houston, TX, 77030, United States.
Department of Medicine, Center for Bioenergetics, Houston Methodist Research Institute, 6670 Bertner Avenue, Houston, TX, 77030, United States.
Lipids. 2020 Jul;55(4):299-307. doi: 10.1002/lipd.12237. Epub 2020 Apr 7.
Moderate alcohol consumption is associated with increased plasma high-density lipoprotein (HDL)-cholesterol concentrations and reduced risk for cardiovascular disease. Plasma cholesteryl ester transfer activity (CETA) mediates the exchange of HDL-cholesteryl ester (CE) for the triacylglycerol (TAG) of very-low-density lipoproteins. We compared the effects of oral challenges of Alcohol, saturated fat (SAT), and (Alcohol + SAT) on plasma CETA, cholesterol, nonesterified fatty acids (NEFA), and TAG among normo-triglyceridemic (NTG) and mildly hypertriglyceridemic (HTG) volunteers having a range of plasma TAG concentrations. The major changes were (1) CETA increased more after ingestion of SAT and (Alcohol + SAT) in the HTG group versus the NTG group; (2) after all three challenges, elevation of plasma TAG concentration persisted longer in the HTG versus NTG group. Plasma cholesterol was not affected by the three dietary challenges, while Alcohol increased NEFA more in the HTG group than the NTG group. Plasma TAG best predicted plasma CETA, suggesting that intestinally derived lipoproteins are acceptors of HDL-CE. Unexpectedly, ingestion of (Alcohol + SAT) reduced the strength of the correlation between plasma TAG and CETA, that is the effects of (SAT and Alcohol) on plasma CETA are not synergistic nor additive but rather mutually suppressive. The alcohol-mediated inhibition of CE-transfer to chylomicrons maintains a higher plasma HDL-cholesterol concentration, which is athero-protective, although the suppressive metabolite underlying this correlation could be acetate, the terminal alcohol metabolite, other factors, including CETA inhibitors, are also likely important.
适量饮酒可使血浆高密度脂蛋白(HDL)胆固醇浓度升高,并降低心血管疾病风险。血浆胆固醇酯转移蛋白(CETA)介导 HDL 胆固醇酯(CE)与极低密度脂蛋白的三酰甘油(TAG)的交换。我们比较了酒精、饱和脂肪(SAT)和(酒精+SAT)口服挑战对具有不同血浆 TAG 浓度的正常甘油三酯血症(NTG)和轻度高甘油三酯血症(HTG)志愿者血浆 CETA、胆固醇、非酯化脂肪酸(NEFA)和 TAG 的影响。主要变化有:(1)在 HTG 组,SAT 和(酒精+SAT)摄入后 CETA 增加较 NTG 组更多;(2)在所有三种挑战后,HTG 组血浆 TAG 浓度升高持续时间较 NTG 组更长。三种饮食挑战均不影响血浆胆固醇,而酒精使 HTG 组的 NEFA 升高较 NTG 组更明显。血浆 TAG 最好地预测了血浆 CETA,表明肠源性脂蛋白是 HDL-CE 的接受体。出乎意料的是,(酒精+SAT)的摄入降低了血浆 TAG 和 CETA 之间相关性的强度,即(SAT 和酒精)对血浆 CETA 的影响不是协同或相加的,而是相互抑制的。酒精介导的 CE 向乳糜微粒的转移抑制作用维持了更高的血浆 HDL 胆固醇浓度,这是动脉粥样硬化保护作用,尽管这种相关性的抑制代谢物可能是醋酸盐,即终末酒精代谢物,其他因素,包括 CETA 抑制剂,也可能很重要。