Sanford Research, Sioux Falls, SD, USA; Sanford School of Medicine, University of South Dakota, Sioux Falls, SD, USA; The Pennsylvania State University, Department of Nutritional Sciences, University Park, PA, USA.
The Pennsylvania State University, Department of Nutritional Sciences, University Park, PA, USA; West Coast Metabolomics Center, UC Davis Genome Center, University of California Davis, CA, USA.
Prostaglandins Leukot Essent Fatty Acids. 2018 Jan;128:1-10. doi: 10.1016/j.plefa.2017.10.006. Epub 2017 Nov 11.
Metabolic syndrome (MetSyn) is characterized by chronic inflammation which mediates the associated high risk for cardiovascular and other diseases. Oxylipins are a superclass of lipid mediators with potent bioactivities in inflammation, vascular biology, and more. While their role as locally produced agents is appreciated, most oxylipins in plasma are found in lipoproteins suggesting defective regulation of inflammation could be mediated by the elevated VLDL and low HDL levels characteristic of MetSyn. Our objective was to compare the oxylipin composition of VLDL, LDL, and HDL in 14 optimally healthy individuals and 31 MetSyn patients, and then to determine the effects of treating MetSyn subjects with 4g/day of prescription omega-3 fatty acids (P-OM3) on lipoprotein oxylipin profiles. We compared oxylipin compositions of healthy (14) and MetSyn (31) subjects followed by randomization and assignment to 4g/d P-OM3 for 16 weeks using LC/MS/MS. Compared to healthy subjects, MetSyn is characterized by abnormalities of (1) pro-inflammatory, arachidonate-derived oxylipins from the lipoxygenase pathway in HDL; and (2) oxylipins mostly not derived from arachidonate in VLDL. P-OM3 treatment corrected many components of these abnormalities, reducing the burden of inflammatory mediators within peripherally circulating lipoproteins that could interfere with, or enhance, local effectors of inflammatory stress. We conclude that MetSyn is associated with a disruption of lipoprotein oxylipin patterns consistent with greater inflammatory stress, and the partial correction of these dysoxylipinemias by treatment with omega-3 fatty acids could explain some of their beneficial effects.
代谢综合征（MetSyn）的特征是慢性炎症，这介导了与心血管和其他疾病相关的高风险。氧化脂类是一类脂质介质超类，具有在炎症、血管生物学等方面的强大生物活性。虽然它们作为局部产生的物质的作用已被认识到，但大多数血浆中的氧化脂类存在于脂蛋白中，这表明代谢综合征特有的 VLDL 升高和 HDL 降低可能介导了炎症的调节缺陷。我们的目的是比较 14 名最佳健康个体和 31 名代谢综合征患者的 VLDL、LDL 和 HDL 中的氧化脂类组成，然后确定用 4g/天处方ω-3 脂肪酸（P-OM3）治疗代谢综合征患者对脂蛋白氧化脂类谱的影响。我们比较了健康（14 名）和代谢综合征（31 名）受试者的氧化脂类组成，然后进行随机分组，并在 16 周内用 LC/MS/MS 分配到每天 4g 的 P-OM3。与健康受试者相比，代谢综合征的特征是（1）HDL 中来自脂氧合酶途径的促炎、花生四烯酸衍生的氧化脂类异常；和（2）VLDL 中主要不是来自花生四烯酸的氧化脂类异常。P-OM3 治疗纠正了这些异常的许多成分，减少了外周循环脂蛋白中炎症介质的负担，这些炎症介质可能干扰或增强炎症应激的局部效应物。我们得出结论，代谢综合征与脂蛋白氧化脂类模式的破坏一致，提示炎症应激增加，而用 ω-3 脂肪酸治疗对这些氧化脂类失调的部分纠正可以解释其部分有益作用。
