Dietary High-Fat Promotes Cognitive Impairment by Suppressing Mitophagy

作者全名："Wen, Jie; Wang, Yangyang; Wang, Chuanling; Yuan, Minghao; Chen, Fei; Zou, Qian; Cai, Zhiyou; Zhao, Bin"

作者地址："[Wen, Jie; Zhao, Bin] Guangdong Med Univ, Dept & Inst Neurol, Zhanjiang 524001, Guangdong, Peoples R China; [Wen, Jie; Zhao, Bin] Guangdong Key Lab Aging Related Cardiac & Cerebral, Zhanjiang 524001, Guangdong, Peoples R China; [Wen, Jie; Wang, Yangyang; Wang, Chuanling; Yuan, Minghao; Chen, Fei; Zou, Qian; Cai, Zhiyou] Chongqing Key Lab Neurodegenerat Dis, Chongqing 400013, Peoples R China; [Wen, Jie; Wang, Yangyang; Wang, Chuanling; Yuan, Minghao; Chen, Fei; Zou, Qian; Cai, Zhiyou] Chongqing Gen Hosp, Dept Neurol, Chongqing 400013, Peoples R China; [Wang, Chuanling; Yuan, Minghao; Chen, Fei] Chongqing Med Univ, Chongqing 400016, Peoples R China"

通信作者："Zhao, B (通讯作者)，Guangdong Med Univ, Dept & Inst Neurol, Zhanjiang 524001, Guangdong, Peoples R China.; Zhao, B (通讯作者)，Guangdong Key Lab Aging Related Cardiac & Cerebral, Zhanjiang 524001, Guangdong, Peoples R China.; Cai, ZY (通讯作者)，Chongqing Key Lab Neurodegenerat Dis, Chongqing 400013, Peoples R China.; Cai, ZY (通讯作者)，Chongqing Gen Hosp, Dept Neurol, Chongqing 400013, Peoples R China."

来源：OXIDATIVE MEDICINE AND CELLULAR LONGEVITY

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:000921564900004

JCR分区：Q2

影响因子：7.31

年份：2023

卷号：2023

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：　

摘要："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 mu M). 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."

基金机构：Chongqing Health Construction Commission's Unit Capacity Improvement Program Construction Project [(2019NLTS001)-ZS03174]; Operating Funds of Chongqing Key Laboratory of Neurodegenerative Diseases [1000013]; Chongqing Talent Project [2000062]; High-Level Talent Introduction Plan [2000055]; Chongqing Postdoctoral Science Foundation [CSTB2022NSCQ-BHX0634]; International Student Talent Venture Fund [2000079]

基金资助正文："This work was supported by the Chongqing Health Construction Commission's Unit Capacity Improvement Program Construction Project (2019NLTS001)-ZS03174, Operating Funds of Chongqing Key Laboratory of Neurodegenerative Diseases (1000013), Chongqing Talent Project (2000062), High-Level Talent Introduction Plan (2000055), Chongqing Postdoctoral Science Foundation (CSTB2022NSCQ-BHX0634), and International Student Talent Venture Fund (2000079)."