Modest diet-induced weight loss reduces macrophage cholesterol efflux to plasma of patients with metabolic syndrome.
Modest diet-induced weight loss reduces macrophage cholesterol efflux to plasma of patients with metabolic syndrome.
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DOI：
10.1016/j.jacl.2013.05.004
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发表时间：
2013-11
影响因子：
4.4
通讯作者：
Pownall HJ
中科院分区：
文献类型：
--
作者：
Vasudevan M;Tchoua U;Gillard BK;Jones PH;Ballantyne CM;Pownall HJ
肥胖相关代谢综合征（MetS）与血脂异常有关，包括高脂血症和低血浆高密度脂蛋白胆固醇（HDL-C）。HDL通过巨噬细胞胆固醇流出（MCE）启动胆固醇逆向转运（RCT）。一些人假设血脂异常患者RCT受损。患者血浆MCE（HDL功能指标）与动脉粥样硬化负荷呈负相关。特别是，高脂血症者血浆MCE高于正常脂血症者。虽然减肥可以降低血脂异常，但其对肥胖代谢综合征患者血浆MCE的影响尚不清楚。因此，我们测试了以下假设：减轻血脂异常伴随体重减轻使MetS血浆的MCE能力降低至NL血浆的MCE能力。测量了减肥前后来自NL对照和肥胖MetS患者的THP-1巨噬细胞至血浆的胆固醇流出量（MCE）。肥胖、代谢综合征患者血浆MCE高于对照血浆（p=0.006）。MetS患者的体重减轻（平均=-9.77 kg）降低了血脂异常、胰岛素抵抗和收缩压。HDL-C无变化，载脂蛋白A-I随体重减轻而降低。MetS患者的体重减轻使MCE（p<0.001）与NL受试者的MCE标准化。MCE与载脂蛋白B水平相关（r2 = 0.13 - 0.38）。层析显示，巨噬细胞胆固醇最初与HDL结合，但随后在含载脂蛋白B的脂蛋白中积累。虽然巨噬细胞胆固醇流出的初始受体是HDL，但升高的载脂蛋白B脂蛋白是增加MetS患者MCE的胆固醇汇。体重减轻导致MetS患者的载脂蛋白B-脂蛋白降低和血浆MCE降低。
Obesity-linked metabolic syndrome (MetS) is associated with a dyslipidemic profile that includes hypertriglyceridemia and low plasma high-density lipoprotein cholesterol (HDL-C). HDL initiates reverse cholesterol transport (RCT) via macrophage cholesterol efflux (MCE). Some hypothesize that dyslipidemic patients have impaired RCT. MCE to patient plasma, a metric of HDL function, inversely correlates with atherosclerotic burden. Paradoxically, MCE to plasma of hypertriglyceridemic subjects is higher than that to normolipidemic (NL) plasma. Although weight-loss reduces dyslipidemia, its effect on MCE to the plasma of obese, MetS patients is unknown. Thus, we tested the hypothesis that reducing dyslipidemia with weight-loss reduces the MCE capacity of MetS plasma to that of NL plasma. Cholesterol efflux (MCE) from THP-1 macrophages to plasma from NL controls and to obese, MetS patients before and after weight-loss was measured. MCE to plasma of obese, MetS patients was higher than that to control plasma (p=0.006). Weight-loss in MetS patients (mean = −9.77 kg) reduced dyslipidemia, insulin resistance and systolic blood pressure. HDL-C was unchanged and apolipoprotein A-I decreased with weight-loss. Weight-loss in MetS patients normalized MCE (p<0.001) to that of NL subjects. MCE correlated with apolipoprotein B levels (r2 = 0.13 – 0.38). Chromatography showed that macrophage cholesterol initially associates with HDL but accumulates in apolipoprotein B-containing lipoproteins at later times. While the initial acceptor of macrophage cholesterol efflux is HDL, the elevated apo B lipoproteins are a cholesterol sink that increase MCE in MetS patients. Weight loss results in decreased apo B-lipoproteins and decreased MCE to plasma of MetS patients.
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影响因子：
6.5
作者：
Sankaranarayanan, Sandhya;Oram, John F.;Asztalos, Bela F.;Vaughan, Ashley M.;Lund-Katz, Sissel;Adorni, Maria Pia;Phillips, Michael C.;Rothblat, George H.
通讯作者：
Rothblat, George H.
影响因子：
5.3
作者：
Tchoua, Urbain;Gillard, Baiba K.;Pownall, Henry J.
通讯作者：
Pownall, Henry J.
影响因子：
2.9
作者：
Pownall, Henry J.
通讯作者：
Pownall, Henry J.
影响因子：
5.3
作者：
Attia, Nesrine;Ramaharo, Angela;Fournier, Natalie
通讯作者：
Fournier, Natalie
影响因子：
9.7
作者：
Loehr, Laura R.;Rosamond, Wayne D.;Heiss, Gerardo
通讯作者：
Heiss, Gerardo