Department of Medicine, University of Illinois at Chicago, Chicago, IL.
Department of Neurology Rush University, Chicago, IL.
J Lipid Res. 2019 Mar;60(3):566-578. doi: 10.1194/jlr.M090464. Epub 2018 Dec 10.
EPA and DHA protect against multiple metabolic and neurologic disorders. Although DHA appears more effective for neuroinflammatory conditions, EPA is more beneficial for depression. However, the brain contains negligible amounts of EPA, and dietary supplements fail to increase it appreciably. We tested the hypothesis that this failure is due to absorption of EPA as triacylglycerol, whereas the transporter at the blood-brain barrier requires EPA as lysophosphatidylcholine (LPC). We compared tissue uptake in normal mice gavaged with equal amounts (3.3 μmol/day) of either LPC-EPA or free EPA (surrogate for current supplements) for 15 days and also measured target gene expression. Compared with the no-EPA control, LPC-EPA increased brain EPA >100-fold (from 0.03 to 4 μmol/g); free EPA had little effect. Furthermore, LPC-EPA, but not free EPA, increased brain DHA 2-fold. Free EPA increased EPA in adipose tissue, and both supplements increased EPA and DHA in the liver and heart. Only LPC-EPA increased EPA and DHA in the retina, and expression of brain-derived neurotrophic factor, cyclic AMP response element binding protein, and 5-hydroxy tryptamine (serotonin) receptor 1A in the brain. These novel results show that brain EPA can be increased through diet. Because LPC-EPA increased both EPA and DHA in the brain, it may help in the treatment of depression as well as neuroinflammatory diseases, such as Alzheimer's disease.
EPA 和 DHA 可预防多种代谢和神经紊乱。尽管 DHA 似乎对神经炎症更为有效,但 EPA 对抑郁症更有益。然而,大脑中几乎不含 EPA,而且膳食补充剂也不能显著增加其含量。我们检验了这样一种假设,即这种失败是由于 EPA 被吸收为三酰基甘油,而血脑屏障的转运体需要 EPA 作为溶血磷脂酰胆碱(LPC)。我们比较了正常小鼠在灌胃 15 天后给予等量(3.3 μmol/天)的 LPC-EPA 或游离 EPA(代表当前的补充剂)的组织摄取情况,并测量了靶基因表达。与无 EPA 对照组相比,LPC-EPA 使大脑中的 EPA 增加了>100 倍(从 0.03 增加到 4 μmol/g);游离 EPA 几乎没有效果。此外,LPC-EPA 而非游离 EPA 使大脑中的 DHA 增加了两倍。游离 EPA 增加了脂肪组织中的 EPA,两种补充剂都增加了肝脏和心脏中的 EPA 和 DHA。只有 LPC-EPA 增加了视网膜中的 EPA 和 DHA,以及大脑中脑源性神经营养因子、环磷酸腺苷反应元件结合蛋白和 5-羟色胺(血清素)受体 1A 的表达。这些新的结果表明,通过饮食可以增加大脑中的 EPA。由于 LPC-EPA 增加了大脑中的 EPA 和 DHA,它可能有助于治疗抑郁症以及神经炎症性疾病,如阿尔茨海默病。