Division of Neuroscience, School of Pharmacy, Iwate Medical University, 1-1-1 Idaidori, Yahaba-cho, Shiwa-gun, Iwate, 028-3694, Japan.
Laboratory of Molecular and Cellular Biochemistry, Graduates School of Pharmaceutical Sciences, Tohoku University, Sendai, Miyagi, Japan.
Sci Rep. 2021 May 12;11(1):9749. doi: 10.1038/s41598-021-88870-9.
Conjugated linoleic acid (CLA) is an isomer of linoleic acid (LA). The predominant dietary CLA is cis-9, trans-11-CLA (c-9, t-11-CLA), which constitutes up to ~ 90% of total CLA and is thought to be responsible for the positive health benefits associated with CLA. However, the effects of c-9, t-11-CLA on Alzheimer's disease (AD) remain to be elucidated. In this study, we investigated the effect of dietary intake of c-9, t-11-CLA on the pathogenesis of an AD mouse model. We found that c-9, t-11-CLA diet-fed AD model mice significantly exhibited (1) a decrease in amyloid-β protein (Aβ) levels in the hippocampus, (2) an increase in the number of microglia, and (3) an increase in the number of astrocytes expressing the anti-inflammatory cytokines, interleukin-10 and 19 (IL-10, IL-19), with no change in the total number of astrocytes. In addition, liquid chromatography-tandem mass spectrometry (LC-MS/MS) and gas chromatographic analysis revealed that the levels of lysophosphatidylcholine (LPC) containing c-9, t-11-CLA (CLA-LPC) and free c-9, t-11-CLA were significantly increased in the brain of c-9, t-11-CLA diet-fed mice. Thus, dietary c-9, t-11-CLA entered the brain and appeared to exhibit beneficial effects on AD, including a decrease in Aβ levels and suppression of inflammation.
共轭亚油酸(CLA)是亚油酸(LA)的异构体。饮食中主要的 CLA 异构体是顺式-9,反式-11-CLA(c-9,t-11-CLA),其构成了高达~90%的总 CLA,被认为是与 CLA 相关的积极健康益处的原因。然而,c-9,t-11-CLA 对阿尔茨海默病(AD)的影响仍有待阐明。在这项研究中,我们研究了饮食摄入 c-9,t-11-CLA 对 AD 小鼠模型发病机制的影响。我们发现,c-9,t-11-CLA 饮食喂养的 AD 模型小鼠显著表现出:(1)海马中淀粉样β蛋白(Aβ)水平降低;(2)小胶质细胞数量增加;(3)表达抗炎细胞因子白细胞介素-10 和 19(IL-10、IL-19)的星形胶质细胞数量增加,而星形胶质细胞总数无变化。此外,液相色谱-串联质谱(LC-MS/MS)和气相色谱分析表明,含有 c-9,t-11-CLA(CLA-LPC)和游离 c-9,t-11-CLA 的溶血磷脂酰胆碱(LPC)水平在 c-9,t-11-CLA 饮食喂养的小鼠脑中显著增加。因此,饮食中的 c-9,t-11-CLA 进入大脑,似乎对 AD 具有有益作用,包括降低 Aβ 水平和抑制炎症。