Nakato Mitsuhiro, Matsuo Michinori, Kono Nozomu, Arita Makoto, Arai Hiroyuki, Ogawa Jun, Kioka Noriyuki, Ueda Kazumitsu
Division of Applied Life Sciences, Kyoto University Graduate School of Agriculture, Kyoto 606-8502, Japan.
Department of Food and Nutrition, Faculty of Home Economics, Kyoto Women's University, Kyoto 605-8501, Japan.
J Lipid Res. 2015 Oct;56(10):1880-90. doi: 10.1194/jlr.M058164. Epub 2015 Aug 3.
PUFAs, which account for 25-30% of the total fatty acids in the human brain, are important for normal brain development and cognitive function. However, it remains unclear how PUFAs are delivered to neurons and exert their effects. In this study, we demonstrated that n-3 and n-6 PUFAs added to the medium are incorporated into membrane phospholipids of primary glial cells from rat cortices, and then secreted as the fatty acid moiety of phospholipids in apoE-containing lipoproteins (LpEs). Tandem mass spectrometry analysis further showed that LpEs secreted from glial cells contain a variety of metabolites of PUFAs produced in glial cells by elongation and unsaturation. LpEs are absorbed by endocytosis into neurons via LDL receptor-related protein 1. LpE-containing n-3 and n-6 PUFAs exhibit a strong effect on neurite outgrowth of hippocampal neurons by increasing the number of branches. This study sheds light on the novel role of LpEs in the central nervous system and also a novel pathway in which PUFAs act on neurons.
多不饱和脂肪酸（PUFAs）占人类大脑总脂肪酸的25%-30%，对正常大脑发育和认知功能至关重要。然而，目前尚不清楚PUFAs是如何传递给神经元并发挥其作用的。在本研究中，我们证明添加到培养基中的n-3和n-6 PUFAs被整合到大鼠皮质原代神经胶质细胞的膜磷脂中，然后作为含载脂蛋白E的脂蛋白（LpEs）中磷脂的脂肪酸部分分泌出来。串联质谱分析进一步表明，神经胶质细胞分泌的LpEs含有多种由神经胶质细胞通过延长和去饱和作用产生的PUFAs代谢产物。LpEs通过低密度脂蛋白受体相关蛋白1以内吞作用被神经元吸收。含LpE的n-3和n-6 PUFAs通过增加分支数量对海马神经元的轴突生长产生强烈影响。这项研究揭示了LpEs在中枢神经系统中的新作用，以及PUFAs作用于神经元的新途径。
