Department of Food Science and Technology, College of Agriculture and Environmental Sciences, University of California, One Shields Avenue, Davis, CA, 95616, USA.
Brain Physiology and Metabolism Section, Laboratory of Neuroscience, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
Mol Neurobiol. 2017 Aug;54(6):4303-4315. doi: 10.1007/s12035-016-9968-1. Epub 2016 Jun 23.
Linoleic acid (LA, 18:2n-6) is a precursor to arachidonic acid (AA, 20:4n-6), which can be converted by brain lipoxygenase and cyclooxygenase (COX) enzymes into various lipid mediators involved in the regulation of brain immunity. Brain AA metabolism is activated in rodents by the bacterial endotoxin, lipopolysaccharide (LPS). This study tested the hypothesis that dietary LA lowering, which limits plasma supply of AA to the brain, reduces LPS-induced upregulation in brain AA metabolism. Male Fischer CDF344 rats fed an adequate LA (5.2 % energy (en)) or low LA (0.4 % en) diet for 15 weeks were infused with LPS (250 ng/h) or vehicle into the fourth ventricle for 2 days using a mini-osmotic pump. The incorporation rate of intravenously infused unesterified C-AA into brain lipids, eicosanoids, and activities of phospholipase A and COX-1 and 2 enzymes were measured. Dietary LA lowering reduced the LPS-induced increase in prostaglandin E concentration and COX-2 activity (P < 0.05 by two-way ANOVA) without altering phospholipase activity. The C-AA incorporation rate into brain lipids was decreased by dietary LA lowering (P < 0.05 by two-way ANOVA). The present findings suggest that dietary LA lowering reduced LPS-induced increase in brain markers of AA metabolism. The clinical utility of LA lowering in brain disorders should be explored in future studies.
亚油酸（LA，18:2n-6）是花生四烯酸（AA，20:4n-6）的前体，AA 可通过脑脂氧合酶和环氧化酶（COX）酶转化为参与脑免疫调节的各种脂质介质。细菌内毒素脂多糖（LPS）激活啮齿动物的脑 AA 代谢。本研究检验了这样一个假设，即降低饮食中的 LA（限制 AA 向大脑的血浆供应）可降低 LPS 诱导的脑 AA 代谢上调。15 周内，雄性 Fischer CDF344 大鼠喂食充足 LA（5.2%能量（en））或低 LA（0.4%en）饮食，然后通过微型渗透泵将 LPS（250ng/h）或载体注入第四脑室 2 天。静脉内输注的未酯化 C-AA 掺入脑脂质、类二十烷酸和磷脂酶 A 和 COX-1 和 2 酶活性的掺入率。饮食中的 LA 降低减少了前列腺素 E 浓度和 COX-2 活性的 LPS 诱导增加（通过双向 ANOVA 为 P<0.05），而不改变磷脂酶活性。脑脂质中 C-AA 的掺入率因饮食中的 LA 降低而降低（通过双向 ANOVA 为 P<0.05）。本研究结果表明，饮食中的 LA 降低减少了 LPS 诱导的脑 AA 代谢标志物的增加。未来的研究应该探讨 LA 降低在脑疾病中的临床应用。
