From the Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia (A.A.K., P.A.M., N.E.S., P.J.N., G.W., R.T., K.H., T.W.N., N.A.M., J.M.W., C.K.B., Z.H.A., G.W.L., B.A.K., P.J.M.); Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Victoria, Australia (A.A.K., B.A.K., P.J.M.); Faculty of Applied Medical Sciences, Umm Al-Qura University, Makkah, Saudi Arabia (A.A.K.); King Fahad Medical City, Riyadh, Saudi Arabia (Z.H.A.); and School of Biomedical Sciences, University of Western Australia, Perth (T.W.N.).
Arterioscler Thromb Vasc Biol. 2018 Feb;38(2):438-447. doi: 10.1161/ATVBAHA.117.310212. Epub 2017 Dec 28.
High-density lipoprotein (HDL) lipid composition and function may better reflect cardiovascular risk than HDL cholesterol concentration. This study characterized the relationships between HDL composition, metabolism, and function in metabolic syndrome (MetS) patients and how changes in composition after weight loss (WL) and exercise treatments are related to function.
Plasma samples from MetS patients (n=95) and healthy individuals (n=40) were used in this study. Subsets of the MetS group underwent 12 weeks of no treatment (n=17), WL (n=19), or WL plus exercise (WLEX; n=17). HDL was isolated using density-gradient ultracentrifugation. The HDL lipidome was analyzed by mass spectrometry, and particle size determined by nuclear magnetic resonance. Cholesteryl ester transfer protein activity and ex vivo HDL cholesterol efflux capacity (CEC) were assessed. The HDL lipidome in the MetS patients was substantially different from that in healthy individuals, mean particle size was smaller, and CEC was lower. Several HDL phospholipid and sphingolipid species were associated with HDL diameter and CEC. The HDL lipidome and particle size were modified toward the healthy individuals after WL and WLEX treatments, with greater effects observed in the latter group. Cholesteryl ester transfer protein activity was reduced after WL and WLEX, and CEC was improved after WLEX.
WLEX treatment in MetS patients normalizes the HDL lipidome and particle size profile and enhances CEC. HDL lipids associated with diminished CEC may represent novel biomarkers for early prediction of HDL dysfunction and disease risk and may represent potential therapeutic targets for future HDL therapies.
URL: http://www.clinicaltrials.gov. Unique identifier: NCT00163943.
高密度脂蛋白（HDL）的脂质组成和功能可能比 HDL 胆固醇浓度更能反映心血管风险。本研究旨在描述代谢综合征（MetS）患者的 HDL 组成、代谢和功能之间的关系，以及减肥（WL）和运动治疗后组成的变化与功能的关系。
本研究使用了 MetS 患者（n=95）和健康个体（n=40）的血浆样本。MetS 组的一部分患者未接受治疗（n=17）、接受 WL（n=19）或 WL 加运动（WLEX；n=17）治疗 12 周。使用密度梯度超速离心法分离 HDL。通过质谱分析法分析 HDL 脂质组，通过核磁共振法测定颗粒大小。评估胆固醇酯转移蛋白活性和体外 HDL 胆固醇流出能力（CEC）。MetS 患者的 HDL 脂质组与健康个体明显不同，平均颗粒直径较小，CEC 较低。几种 HDL 磷脂和鞘脂与 HDL 直径和 CEC 相关。经过 WL 和 WLEX 治疗后，MetS 患者的 HDL 脂质组和颗粒大小向健康个体的方向发生了改变，后者的效果更为显著。WL 和 WLEX 治疗后，胆固醇酯转移蛋白活性降低，CEC 改善。
MetS 患者的 WLEX 治疗可使 HDL 脂质组和颗粒大小谱正常化，并增强 CEC。与 CEC 降低相关的 HDL 脂质可能代表预测 HDL 功能障碍和疾病风险的新型生物标志物，也可能代表未来 HDL 治疗的潜在治疗靶点。
