Dietary omega-3 fatty acids modulate the eicosanoid profile in man primarily via the CYP-epoxygenase pathway
Dietary omega-3 fatty acids modulate the eicosanoid profile in man primarily via the CYP-epoxygenase pathway
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DOI：
10.1194/jlr.m047357
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发表时间：
2014-06-01
影响因子：
6.5
通讯作者：
Schunck, Wolf-Hagen
中科院分区：
文献类型：
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作者：
Fischer, Robert;Konkel, Anne;Schunck, Wolf-Hagen
花生四烯酸（AA）的细胞色素P450（CYP 450）依赖性代谢产物参与心血管功能的调节。辅酶A酶也接受EPA和DHA以产生更有效的血管扩张和潜在的抗血管代谢物，这表明内源性CYP-类二十烷酸谱可以通过膳食ω-3脂肪酸有利地改变。为了验证这一假设，20名健康志愿者接受了EPA/DHA补充剂治疗，并分析了由环氧合酶、脂氧合酶（LOX）和CYP依赖性途径产生的AA、EPA和DHA衍生代谢物的循环和尿液水平的伴随变化。将Omega-3指数从约4提高到8主要导致EPA衍生的CYP依赖性环氧代谢物大量增加，随后是EPA和DHA衍生的LOX依赖性单羟基代谢物增加，包括消退素E和D家族的前体;未检测到消退素本身。代谢物/前体脂肪酸比率表明，EPA和DHA的代谢效率分别是AA的8.6倍和2.2倍。对白三烯、前列腺素E、前列环素和血栓素形成的影响仍然相当弱。我们认为，EPA和DHA的CYP依赖性环氧代谢物可能作为介导剂发挥omega-3脂肪酸的血管扩张和心脏保护作用，并可作为临床研究中的生物标志物，调查EPA/DHA补充剂的心血管作用。
Cytochrome P450 (CYP)-dependent metabolites of arachidonic acid (AA) contribute to the regulation of cardiovascular function. CYP enzymes also accept EPA and DHA to yield more potent vasodilatory and potentially anti-arrhythmic metabolites, suggesting that the endogenous CYP-eicosanoid profile can be favorably shifted by dietary omega-3 fatty acids. To test this hypothesis, 20 healthy volunteers were treated with an EPA/DHA supplement and analyzed for concomitant changes in the circulatory and urinary levels of AA-, EPA-, and DHA-derived metabolites produced by the cyclooxygenase-, lipoxygenase (LOX)-, and CYP-dependent pathways. Raising the Omega-3 Index from about four to eight primarily resulted in a large increase of EPA-derived CYP-dependent epoxy-metabolites followed by increases of EPA-and DHA-derived LOX-dependent monohydroxy-metabolites including the precursors of the resolvin E and D families; resolvins themselves were not detected. The metabolite/precursor fatty acid ratios indicated that CYP epoxygenases metabolized EPA with an 8.6-fold higher efficiency and DHA with a 2.2-fold higher efficiency than AA. Effects on leukotriene, prostaglandin E, prostacyclin, and thromboxane formation remained rather weak. We propose that CYP-dependent epoxy-metabolites of EPA and DHA may function as mediators of the vasodilatory and cardioprotective effects of omega-3 fatty acids and could serve as biomarkers in clinical studies investigating the cardiovascular effects of EPA/DHA supplementation.