生活方式干预仅在正常低密度脂蛋白胆固醇血浆水平下增强代谢综合征患者的高密度脂蛋白功能。

Lifestyle intervention enhances high-density lipoprotein function among patients with metabolic syndrome only at normal low-density lipoprotein cholesterol plasma levels.

机构信息

Département d'Endocrinologie, Diabétologie et Nutrition, DHU FIRE, Hôpital Bichat, Assistance Publique-Hôpitaux de Paris, France; INSERM U1138, Centre de Recherche des Cordeliers, Paris, France; Université Paris-Diderot, Paris 7, Paris, France.

Service de Biochimie Métabolique, Groupe hospitalier Pitié-Salpêtrière-Charles Foix, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France; INSERM UMRS 1166 ICAN, Université Pierre et Marie Curie Paris 6, Hôpital de la Pitie, Paris, France; Faculté de Pharmacie, Université Paris Descartes, Paris, France.

出版信息

J Clin Lipidol. 2016 Sep-Oct;10(5):1172-81. doi: 10.1016/j.jacl.2016.05.008. Epub 2016 May 14.

DOI:10.1016/j.jacl.2016.05.008

PMID:27678434

Abstract

BACKGROUND

Metabolic syndrome (MetS) is associated with altered lipoprotein metabolism and impairment in the functionality of small, dense high-density lipoprotein (HDL) particles secondary to compositional alterations.

OBJECTIVE

The objective of this study was to investigate the capacity of a lifestyle program to improve the composition and antioxidative function (AOX) of small dense HDL3c in MetS.

METHODS

Patients with MetS (n = 33) not taking lipid-lowering drugs were recruited to follow a 12-week educational program to reduce caloric intake and to increase physical activity. HDL subfractions were preparatively isolated by isopycnic density-gradient ultracentrifugation. AOX of HDL3c was assessed as its capacity to inhibit low-density lipoprotein oxidation induced by an azoinitiator.

RESULTS

AOX of HDL3c was significantly improved (mean reduction in the propagation rate of low-density lipoprotein oxidation by HDL3c, -6.8%, P = .03) and systemic oxidative stress, assessed as plasma levels of 8-isoprostanes, tended to decrease in normocholesterolemic MetS patients (low-density lipoprotein cholesterol [LDL-C] < 130 mg/dL) but not in patients with elevated LDL-C levels and in the whole study population. In both the whole study population and the normocholesterolemic subgroup, lifestyle intervention resulted in a significant degree of normalization of HDL3c composition, (enrichment in apolipoprotein A-I and cholesteryl esters, depletion in triglycerides), which was more pronounced at LDL-C < 130 mg/dL.

CONCLUSION

In patients with MetS, a lifestyle program improves AOX of small, dense HDL in subjects with normal LDL-C levels. Correction of HDL composition, involving partial normalization of apoA-I content and core lipid composition, 2 central features of the lipid hydroperoxide-inactivating capacity of HDL, may account for this effect.

摘要

背景

代谢综合征（MetS）与脂蛋白代谢改变以及小而密的高密度脂蛋白（HDL）颗粒功能障碍有关，这是由于其组成改变所致。

目的

本研究旨在探讨生活方式干预对代谢综合征患者小而密的 HDL3c 组成和抗氧化功能（AOX）的改善作用。

方法

招募未服用降脂药物的 MetS 患者（n=33）参加为期 12 周的教育计划，以减少热量摄入并增加身体活动。通过等密度梯度超速离心法对 HDL 亚组分进行预分离。通过其抑制低密度脂蛋白（LDL）被偶氮引发剂诱导氧化的能力来评估 HDL3c 的 AOX。

结果

HDL3c 的 AOX 显著改善（HDL3c 抑制 LDL 氧化的传播速度平均降低了 6.8%，P=0.03），并且在正常胆固醇的 MetS 患者（LDL-C<130mg/dL）中，全身性氧化应激（血浆 8-异前列腺素水平）呈下降趋势，但在 LDL-C 水平升高的患者和整个研究人群中没有。在整个研究人群和正常胆固醇的亚组中，生活方式干预均导致 HDL3c 组成的显著正常化（载脂蛋白 A-I 和胆固醇酯的富集，甘油三酯的消耗），在 LDL-C<130mg/dL 时更为明显。