Zhang Xu, Yang Nan, Ai Ding, Zhu Yi
§Department of Physiology and Pathophysiology, Peking University Health Science Center, Beijing 100191, China.
J Proteome Res. 2015 Apr 3;14(4):1843-53. doi: 10.1021/pr501200u. Epub 2015 Mar 17.
Omega-3 (ω-3) polyunsaturated fatty acids (PUFAs) have beneficial effects in many pathological processes, especially cardiovascular disease, and their protective eicosanoid metabolites are thought to play important roles. However, how ω-3 PUFAs affect the eicosanoid profile has not been elucidated comprehensively. Here, we systematically analyzed the eicosanoid metabolites induced by ω-3 PUFA supplementation. We developed an LC-MS/MS-based method covering 32 arachidonic acid (ARA) metabolites and 37 ω-3 PUFA-derived products. The limits of detection for eicosanoids were between 0.0625 and 1 pg and the detection specificity was optimized. We then quantified eicosanoids in mouse and human plasma and mouse aorta samples after ω-3 PUFA supplementation. Levels of EPA hydroxyl products, 4-HDoHE, 17,18-EEQ, 17,18-DiHETE, TXB2, and LXA4 were significantly changed in both mouse samples, and those of 2-series PGs, EDPs and DHA hydroxyl products were changed in aorta samples. Correlation network analysis of mouse plasma data revealed that some eicosanoids had higher connection degree or betweenness centrality score than others after ω-3 PUFA supplementation. Eicosanoids in human plasma were profiled across five time points after ω-3 PUFA supplementation. Fuzzy c-mean clustering algorithm suggested that the time curves of eicosanoid activity could be described with three kinetic patterns: sustained upregulation, short-term upregulation, and downregulation. This is the first systematic profiling of eicosanoids with ω-3 PUFA supplementation. The highly specific eicosanoid metabolomic and related data analysis methods would be powerful tools for comprehensive eicosanoid study.
ω-3（欧米伽-3）多不饱和脂肪酸（PUFAs）在许多病理过程中具有有益作用，尤其是在心血管疾病方面，其具有保护作用的类二十烷酸代谢产物被认为发挥着重要作用。然而，ω-3多不饱和脂肪酸如何影响类二十烷酸谱尚未得到全面阐明。在此，我们系统地分析了补充ω-3多不饱和脂肪酸后诱导产生的类二十烷酸代谢产物。我们开发了一种基于液相色谱-串联质谱的方法，该方法涵盖32种花生四烯酸（ARA）代谢产物和37种源自ω-3多不饱和脂肪酸的产物。类二十烷酸的检测限在0.0625至1皮克之间，并且检测特异性得到了优化。然后，我们对补充ω-3多不饱和脂肪酸后的小鼠和人血浆以及小鼠主动脉样本中的类二十烷酸进行了定量分析。在两个小鼠样本中，二十碳五烯酸羟基产物、4-羟基二十二碳六烯酸（4-HDoHE）、17,18-环氧二十碳三烯酸（17,18-EEQ）、17,18-二羟二十碳四烯酸（17,18-DiHETE）、血栓素B2（TXB2）和脂氧素A4（LXA4）的水平均发生了显著变化，而在主动脉样本中，2-系列前列腺素、环氧二十碳三烯酸（EDPs）和二十二碳六烯酸羟基产物的水平发生了变化。对小鼠血浆数据的相关网络分析表明，补充ω-3多不饱和脂肪酸后，一些类二十烷酸的连接度或中介中心性得分高于其他类二十烷酸。在补充ω-3多不饱和脂肪酸后的五个时间点对人血浆中的类二十烷酸进行了分析。模糊c均值聚类算法表明，类二十烷酸活性的时间曲线可以用三种动力学模式来描述：持续上调、短期上调和下调。这是首次对补充ω-3多不饱和脂肪酸后的类二十烷酸进行系统分析。高度特异性的类二十烷酸代谢组学及相关数据分析方法将成为全面研究类二十烷酸的有力工具。
