Dietary High-Fat Promotes Cognitive Impairment by Suppressing Mitophagy.
Dietary High-Fat Promotes Cognitive Impairment by Suppressing Mitophagy.
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DOI：
10.1155/2023/4822767
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发表时间：
2023
影响因子：
--
通讯作者：
Zhao, Bin
中科院分区：
文献类型：
--
作者：
Wen, Jie;Wang, Yangyang;Wang, Chuanling;Yuan, Minghao;Chen, Fei;Zou, Qian;Cai, Zhiyou;Zhao, Bin
饮食习惯有助于阿尔茨海默病（AD）和认知障碍的特征，其部分由过度磷酸化的Tau（一种微管相关蛋白）的积累诱导。在小鼠中，富含脂肪的饮食会促进认知功能障碍。然而，膳食脂肪损害大脑的机制仍不清楚。在这项研究中，13个月大的C57 BL/6小鼠被喂食正常或高脂肪饮食（HFD）6个月。用正常培养基或棕榈酸（200 μM）孵育Neuro-2a细胞。利用行为测试评估空间记忆。此外，蛋白质印迹和免疫荧光技术用于确定线粒体自噬相关蛋白的水平。还评估了突触形态和Tau蛋白的磷酸化。给予HFD降低了突触素和脑源性神经营养因子的表达，导致神经元的显著损伤。在体内和体外的不同位点检测到Tau蛋白过度磷酸化。与正常食物喂养的小鼠相比，在喂食HFD的小鼠中观察到学习和记忆能力显著受损，伴有线粒体自噬相关过程受损。总之，高脂肪酸摄入会阻碍线粒体自噬并上调Tau蛋白磷酸化，包括与年龄相关的突触功能障碍，从而导致认知能力下降。
Dietary habits contribute to the characteristics of Alzheimer's disease (AD) and cognitive impairment, which are partly induced by the accumulation of hyperphosphorylated Tau, a microtubule-associated protein. In mice, a fat-rich diet facilitates cognitive dysfunction. However, the mechanism by which dietary fat damages the brain remains unclear. In this study, 13-month-old C57BL/6 mice were fed a normal or high-fat diet (HFD) for 6 months. Neuro-2a cells were incubated with the normal medium or palmitic acid (200 μM). Spatial memory was assessed utilizing a behavioral test. Further, western blotting and immunofluorescence techniques were used to determine the levels of mitophagy-related proteins. The synaptic morphology and phosphorylation of Tau proteins were also evaluated. Administration of HFD decreased the expression of synaptophysin and brain-derived neurotrophic factor expression, leading to significant damage to neurons. Tau protein hyperphosphorylation was detected at different loci both in vivo and in vitro. Significantly impaired learning and memory abilities, accompanied by impaired mitophagy-related processes, were observed in mice fed with HFD as compared to mice fed with normal food. In conclusion, high fatty-acid intake hinders mitophagy and upregulates Tau protein phosphorylation, including age-related synaptic dysfunction, which leads to cognitive decline.
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