Department of Physiology and Neuroscience, University of Southern California Keck School of Medicine, 2250 Alcazar Street, CSC 214, Los Angeles, CA 90089, USA.
Department of Entomology and Nematology, University of California, Davis, CA 95616, USA.
Int J Mol Sci. 2023 Jun 28;24(13):10760. doi: 10.3390/ijms241310760.
Oxylipins, oxidation products of unsaturated free fatty acids (FFAs), are involved in various cellular signaling systems. Among these oxylipins, FFA epoxides are associated with beneficial effects in metabolic and cardiovascular health. FFA epoxides are metabolized to diols, which are usually biologically less active, by soluble epoxide hydrolase (sEH). Plasma epoxide-diol ratios have been used as indirect measures of sEH activity. This study was designed to examine the effects of acute elevation of individual plasma FFAs on a variety of oxylipins, particularly epoxides, diols, and their ratios. We tested if FFA epoxide-diol ratios are altered by circulating FFA levels (i.e., substrate availability) independent of sEH activity. Wistar rats received a constant intravenous infusion of olive (70% oleic acid (OA)), safflower seed (72% linoleic acid (LA)), and fish oils (rich in ω-3 FFAs) as emulsions to selectively raise OA, LA, and ω-3 FFAs (eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)), respectively. As expected, olive, safflower seed, and fish oil infusions selectively raised plasma OA (57%), LA (87%), EPA (70%), and DHA (54%), respectively ( < 0.05 for all). Raising plasma FFAs exerted substrate effects to increase hepatic and plasma epoxide and diol levels. These increases in epoxides and diols occurred to similar extents, resulting in no significant changes in epoxide-diol ratios. These data suggest that epoxide-diol ratios, often used as indices of sEH activity, are not affected by substrate availability or altered plasma FFA levels and that epoxide-diol ratios may be used to compare sEH activity between conditions of different circulating FFA levels.
氧化脂类，不饱和游离脂肪酸（FFA）的氧化产物，参与各种细胞信号系统。在这些氧化脂类中，FFA 环氧化物与代谢和心血管健康的有益作用有关。FFA 环氧化物被可溶的环氧化物水解酶（sEH）代谢为二醇，通常生物活性较低。血浆环氧化物二醇比被用作 sEH 活性的间接测量。本研究旨在检查急性升高个体血浆 FFA 对各种氧化脂类，特别是环氧化物、二醇及其比值的影响。我们测试了 FFA 环氧化物二醇比是否因循环 FFA 水平（即底物可用性）而独立于 sEH 活性而改变。Wistar 大鼠接受橄榄油（70%油酸（OA））、红花籽油（72%亚油酸（LA））和鱼油（富含 ω-3 FFA）的持续静脉输注，以分别选择性地升高 OA、LA 和 ω-3 FFA（二十碳五烯酸（EPA）和二十二碳六烯酸（DHA））。如预期的那样，橄榄油、红花籽油和鱼油输注分别选择性地升高了血浆 OA（57%）、LA（87%）、EPA（70%）和 DHA（54%）（<0.05 所有）。升高血浆 FFA 发挥底物作用，增加肝和血浆环氧化物和二醇水平。这些环氧化物和二醇的增加程度相似，导致环氧化物二醇比没有显著变化。这些数据表明，环氧化物二醇比，通常用作 sEH 活性的指标，不受底物可用性或改变的血浆 FFA 水平的影响，并且环氧化物二醇比可用于比较不同循环 FFA 水平条件下的 sEH 活性。
