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短期高脂肪饮食可调节年轻小鼠海马中的几种炎症、内质网应激和细胞凋亡标志物。

Short-term high-fat diet modulates several inflammatory, ER stress, and apoptosis markers in the hippocampus of young mice.

机构信息

Laboratory of Nutritional Genomics (LabGeN), School of Applied Sciences, University of Campinas (UNICAMP), Limeira, SP, Brazil.

Laboratory of Molecular Biology of Exercise (LaBMEx), School of Applied Sciences, University of Campinas (UNICAMP), Limeira, SP, Brazil.

出版信息

Brain Behav Immun. 2019 Jul;79:284-293. doi: 10.1016/j.bbi.2019.02.016. Epub 2019 Feb 20.

DOI:10.1016/j.bbi.2019.02.016
PMID:30797044
Abstract

The consumption of saturated fatty acids is one of the leading risk factors for Alzheimer's Disease (AD) development. Indeed, the short-term consumption of a high-fat diet (HFD) is related to increased inflammatory signals in the hippocampus; however, the potential molecular mechanisms linking it to AD pathogenesis are not fully elucidated. In our study, we investigated the effects of short-term HFD feeding (within 3, 7 and 10 days) in AD markers and neuroinflammation in the hippocampus of mice. The short period of HFD increased fasting glucose and HOMA-IR. Also, mice fed HFD increased the protein content of β-Amyloid, pTau, TNFα, IL1β, pJNK, PTP1B, peIF2α, CHOP, Caspase3, Cleaved-Caspase3 and Alzheimer-related genes (Bax, PS1, PEN2, Aph1b). At 10 days, both neuronal (N2a) and microglial (BV2) cells presented higher expression of inflammatory and apoptotic genes when stimulated with palmitate. These findings suggest that a short period of consumption of a diet rich in saturated fat is associated with activation of inflammatory, ER stress and apoptotic signals in the hippocampus of young mice.

摘要

饱和脂肪酸的摄入是导致阿尔茨海默病(AD)发生的主要风险因素之一。事实上,短期摄入高脂肪饮食(HFD)与海马体中炎症信号的增加有关;然而,将其与 AD 发病机制联系起来的潜在分子机制尚未完全阐明。在我们的研究中,我们调查了短期 HFD 喂养(3、7 和 10 天内)对小鼠海马体中 AD 标志物和神经炎症的影响。短期 HFD 喂养会增加空腹血糖和 HOMA-IR。此外,喂食 HFD 的小鼠增加了 β-淀粉样蛋白、pTau、TNFα、IL1β、pJNK、PTP1B、peIF2α、CHOP、Caspase3、Cleaved-Caspase3 和与阿尔茨海默病相关的基因(Bax、PS1、PEN2、Aph1b)的蛋白含量。在第 10 天,用软脂酸刺激时,神经元(N2a)和小胶质细胞(BV2)细胞的炎症和凋亡基因表达均升高。这些发现表明,短期摄入富含饱和脂肪的饮食与年轻小鼠海马体中炎症、内质网应激和凋亡信号的激活有关。

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