Medical Department, Division of Gastroenterology, Oncology, Hematology, Rheumatology and Diabetes, Ruppiner Kliniken, Brandenburg Medical School, 16816 Neuruppin, Germany.
Department of Gastroenterology, Sana Klinikum Lichtenberg, 10365 Berlin, Germany.
Int J Mol Sci. 2018 Jan 8;19(1):180. doi: 10.3390/ijms19010180.
Omega-6 polyunsaturated fatty acid (-6 PUFA) is the predominant polyunsaturated fatty acid (PUFA), especially in Western diet. A high omega-6/omega-3 ratio in Western diets is implicated in the development of cardiovascular diseases and inflammatory processes. Studies in animal models and in humans have demonstrated beneficial effects of omega-3 PUFA (-3 PUFA) in a variety of diseases, including cardiac arrhythmias and inflammatory diseases, as well as breast and colon cancer. The molecular mechanisms underlying the effects of -3 PUFA are still not well understood. Possible mechanisms include competition between -3 and -6 PUFAs at the cyclooxygenase (COX) and lipoxygenase (LOX) and cytochrome P450 levels, and subsequent formation of oxylipins with specific anti-inflammatory or anti-arrhythmic effects. In this study, we report the impact of routine long-term treatment with prescription-grade -3 PUFA (either 840 mg or 1680 mg per day) on blood cell membrane fatty acid composition, as well as plasma oxylipin patterns, in a patient population with severe hyperlipidemia and cardiovascular disease who are on standard lipid-lowering and cardioprotective medications. Lipidomics analyses were performed by LC/ESI-MS/MS. Supplementation led to a dose-dependent increase in -3 PUFA eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in the blood cell fraction. We also observed a dose-dependent increase in EPA- and DHA-derived epoxy metabolites, whereas the effect of -3 PUFA supplementation on LOX-dependent EPA- and DHA-derived hydroxy metabolites was less pronounced, with a tendency towards lower metabolites in subjects with higher -3 PUFA levels. These data thus generally confirm effects of -3 PUFA supplementation observed previously in healthy individuals. Additionally, they indicate a suppressive effect of high -3 PUFA supplementation on the formation of LOX metabolites in the context of concomitant aspirin medication.
ω-6 多不饱和脂肪酸（ω-6 PUFA）是主要的多不饱和脂肪酸（PUFA），尤其存在于西方饮食中。高 ω-6/ω-3 比值的西方饮食与心血管疾病和炎症过程的发展有关。动物模型和人类研究表明，ω-3 多不饱和脂肪酸（ω-3 PUFA）对多种疾病有益，包括心律失常和炎症性疾病，以及乳腺癌和结肠癌。ω-3 PUFA 作用的分子机制尚不清楚。可能的机制包括 ω-3 和 ω-6 PUFA 在环氧化酶（COX）和脂氧合酶（LOX）和细胞色素 P450 水平的竞争，以及随后形成具有特定抗炎或抗心律失常作用的氧化脂类。在这项研究中，我们报告了常规长期使用处方级 ω-3 PUFA（每天 840 毫克或 1680 毫克）对严重高脂血症和心血管疾病患者血细胞膜脂肪酸组成以及血浆氧化脂类模式的影响，这些患者正在接受标准的降脂和心脏保护药物治疗。脂质组学分析通过 LC/ESI-MS/MS 进行。补充剂导致血细胞部分中 ω-3 PUFA 二十碳五烯酸（EPA）和二十二碳六烯酸（DHA）呈剂量依赖性增加。我们还观察到 EPA 和 DHA 衍生的环氧代谢物呈剂量依赖性增加，而 ω-3 PUFA 补充对 LOX 依赖性 EPA 和 DHA 衍生的羟基代谢物的影响则不那么明显，高 ω-3 PUFA 水平的受试者中代谢物水平较低。这些数据因此通常证实了先前在健康个体中观察到的 ω-3 PUFA 补充的效果。此外，它们表明在同时服用阿司匹林的情况下，高 ω-3 PUFA 补充对 LOX 代谢物形成具有抑制作用。
