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

Short-term high-fat diet modulates several inflammatory, ER stress, and apoptosis markers in the hippocampus of young mice
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DOI:
10.1016/j.bbi.2019.02.016
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发表时间:
2019-07-01
影响因子:
15.1
通讯作者:
Pauli, Jose Rodrigo
Pauli, Jose Rodrigo
中科院分区:
医学1区
文献类型:
--
作者:
Branco Ramos Nakandakari, Susana Castelo;Munoz, Vitor Rosetto;Pauli, Jose Rodrigo

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饱和脂肪酸的摄入是阿尔茨海默病(AD)发生的主要危险因素之一。事实上,短期摄入高脂饮食(HFD)与海马区炎症信号增加有关;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,我们研究了短期喂养HFD(在3、7和10天内)对小鼠海马区AD标志物和神经炎症的影响。短期高脂饮食可增加空腹血糖和HOMA-IR。此外,喂食HFD的小鼠增加了β-淀粉样蛋白、ptau、肿瘤坏死因子α、白介素1β、pJNK、PTP1B、peIF2α、CHOP、Caspase3、Caspase3和阿尔茨海默病相关基因(Bax、PS1、PEN2、Aph1b)的蛋白质含量。第10天,在棕榈酸酯刺激下,神经细胞(N2a)和小胶质细胞(BV2)都表现出更高的炎症和凋亡基因的表达。这些发现表明,短时间食用富含饱和脂肪的食物与幼鼠海马区炎症、内质网应激和细胞凋亡信号的激活有关。
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 beta-Amyloid, pTau, TNF alpha, IL1 beta, pJNK, PTP1B, peIF2 alpha, 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.