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.
J Clin Lipidol. 2016 Sep-Oct;10(5):1172-81. doi: 10.1016/j.jacl.2016.05.008. Epub 2016 May 14.
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.
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.
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.
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.
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.
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。
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。
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。
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。
在 MetS 患者中，生活方式干预可改善 LDL-C 水平正常的患者小而密的 HDL 的 AOX。这种作用可能与 HDL 脂质过氧化灭活能力的 2 个中心特征（apoA-I 含量和核心脂质组成的部分正常化）有关，涉及到 HDL 组成的纠正。
