Yang Zhi-Hong, Gordon Scott M, Sviridov Denis, Wang Shuibang, Danner Robert L, Pryor Milton, Vaisman Boris, Shichijo Yuka, Doisaki Nobushige, Remaley Alan T
Lipoprotein Metabolism Section, Cardio-Pulmonary Branch, National Heart, Lung and Blood Institute (NHLBI), National Institutes of Health (NIH), Bethesda, MD 20892-1666, USA.
Critical Care Medicine Department, Clinical Center, NIH, Bethesda, MD 20892-1666, USA.
Atherosclerosis. 2017 Jul;262:31-38. doi: 10.1016/j.atherosclerosis.2017.04.017. Epub 2017 Apr 25.
Concentrated fish oils, containing a mixture of long-chain monounsaturated fatty acids (LCMUFA) with aliphatic chains longer than 18 C atoms (i.e., C20:1 and C22:1), have been shown to attenuate atherosclerosis development in mouse models. It is not clear, however, how individual LCMUFA isomers may act on atherosclerosis.
In the present study, we used saury fish oil-derived concentrates enriched in either C20:1 or C22:1 isomer fractions to investigate their individual effect on atherosclerosis and lipoprotein metabolism. LDLR-deficient (LDLr) mice were fed a Western diet supplemented with 5% (w/w) of either C20:1 or C22:1 concentrate for 12 wk.
Compared to the control Western diet with no supplement, both LCMUFA isomers increased hepatic levels of LCMUFA by 2∼3-fold (p < 0.05), and decreased atherosclerotic lesion areas by more than 40% (p < 0.05), although there were no major differences in plasma lipoproteins or hepatic lipid content. Both LCMUFA isomers significantly decreased plasma CRP levels, improved Abca1-dependent cholesterol efflux capacity of apoB-depleted plasma, and enhanced Ppar transcriptional activities in HepG2 cells. LC-MS/MS proteomic analysis of lipoproteins (HDL, LDL and VLDL) revealed that both LCMUFA isomer diets resulted in similar potentially beneficial alterations in proteins involved in complement activation, blood coagulation, and lipid metabolism. Several lipoprotein proteome changes were significantly correlated with atherosclerotic plaque reduction.
Dietary supplementation with the LCMUFA isomers C20:1 or C22:1 was equally effective in reducing atherosclerosis in LDLrmice and this may partly occur through activation of the Ppar signaling pathways and favorable alterations in the proteome of lipoproteins.
浓缩鱼油含有长链单不饱和脂肪酸（LCMUFA）混合物，其脂肪链长于18个碳原子（即C20:1和C22:1），已被证明可减轻小鼠模型中的动脉粥样硬化发展。然而，尚不清楚单个LCMUFA异构体如何作用于动脉粥样硬化。
在本研究中，我们使用富含C20:1或C22:1异构体组分的秋刀鱼油浓缩物，研究它们对动脉粥样硬化和脂蛋白代谢的个体影响。给低密度脂蛋白受体缺陷（LDLr）小鼠喂食添加5%（w/w）C20:1或C22:1浓缩物的西式饮食12周。
与未添加补充剂的对照西式饮食相比，两种LCMUFA异构体均使肝脏中LCMUFA水平升高2至3倍（p < 0.05），并使动脉粥样硬化病变面积减少超过40%（p < 0.05），尽管血浆脂蛋白或肝脏脂质含量没有重大差异。两种LCMUFA异构体均显著降低血浆CRP水平，改善载脂蛋白B耗尽血浆的Abca1依赖性胆固醇流出能力，并增强HepG2细胞中的Ppar转录活性。脂蛋白（HDL、LDL和VLDL）的LC-MS/MS蛋白质组分析表明，两种LCMUFA异构体饮食均导致参与补体激活、血液凝固和脂质代谢的蛋白质发生类似的潜在有益改变。几种脂蛋白蛋白质组变化与动脉粥样硬化斑块减少显著相关。
饮食补充LCMUFA异构体C20:1或C22:1在降低LDLr小鼠动脉粥样硬化方面同样有效，这可能部分通过激活Ppar信号通路以及脂蛋白蛋白质组的有利改变而发生。
