中国病理生理杂志2025，Vol.41Issue(6)：1088-1097,10.DOI:10.3969/j.issn.1000-4718.2025.06.005
早期高脂饮食保护5×FAD小鼠认知功能的脂质组学分析
Lipidomic analysis of protective effect of early high-fat diet on cognition of 5×FAD mice
摘要
Abstract
AIM:To investigate the effects of early high-fat diet(HFD)on cognitive function and hippocam-pal lipidomic profile in transgenic mice bearing five familial Alzheimer disease mutant genes(5×FAD).METHODS:Eight-week-old SPF grade female wild-type(WT)mice were used as the contorl group,and 5×FAD mice were randomly divided into model(5×FAD)group and 5×FAD+HFD group,with 10 mice in each group.The 5×FAD+HFD group was orally given high-fat chow and the remaining 2 groups were given control chow for 12 weeks,and the change in body weight of the mice were recorded.Y-maze and Morris water maze tests were performed to measure the learning memory ability of the mice.Serum total cholesterol(TC),triglyceride(TG),low-density lipoprotein cholesterol(LDL-C)and high-density lipoprotein cholesterol(HDL-C)levels were measured using a biochemical analyzer.Immunohistochemistry was per-formed to visualize amyloid β-protein(Aβ)plaques in brain tissues.Hippocampal levels of tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),IL-6,and Aβ were measured by enzyme-linked immunosorbent assay(ELISA).Non-tar-geted lipidomic technology was used to measure the changes of hippocampal lipids.RESULTS:Compared with WT group,the mice in 5×FAD group lost significantly less weight(P<0.01)and spent significantly less time exploring the new arm of the Y-maze and the target quadrant of the water maze(P<0.05 or P<0.01).Brain Aβ plaques were significant-ly increased(P<0.01).Hippocampal levels of Aβ1-40,Aβ1-42,IL-1β and TNF-α were significantly elevated(P<0.05 or P<0.01).Compared with the 5×FAD group,the mice in the 5×FAD+HFD group showed significant increase in body weight(P<0.01)and time spent exploring the new arm of the Y-maze and the target quadrant of the water maze(P<0.01).Biochmeical analysis showed serum TC,LDL-C,HDL-C levels and HDL/TC ratio were significantly increased(P<0.05).Brain Aβ plaques were significantly reduced(P<0.05)and hippocampal Aβ1-40,Aβ1-42 and IL-1β levels were sig-nificantly decreased(P<0.05).Compared with the WT group,27 lipids were increased and 9 lipids were decreased in the 5×FAD group,involving the pathways such as cholesterol metabolism,fat digestion and absorption,regulation of lipolysis processes in adipocytes,and glycerophospholipid metabolism.Eighteen lipids were increased and 47 lipids were de-creased in the 5×FAD+HFD group compared to the 5×FAD group.Cardiolipin and TG were important lipids for separating the lipid profiles of the WT and 5×FAD groups,and TG was an important lipid for separating the lipid profiles of the 5×FAD and 5×FAD+HFD groups.Differential lipid enrichment analysis showed significant increase in TG lipid in the 5×FAD group compared with the WT group and significant decrease in TG lipid in the 5×FAD+HFD group compared with the 5×FAD group.CONCLUSION:Early HFD ameliorates cognitive function in 5×FAD mice by modifying TG metabolic disorder and attenuating neuroinflammation.关键词
阿尔茨海默病/高脂饮食/脂质组学/认知/神经炎症Key words
Alzheimer disease/high-fat diet/lipidomics/cognition/neuroinflammation分类
临床医学引用本文复制引用
刘天素,廖伟伟,贾鸿伊,韩晓,濮银岩,杨细飞,谢春..早期高脂饮食保护5×FAD小鼠认知功能的脂质组学分析[J].中国病理生理杂志,2025,41(6):1088-1097,10.基金项目
国家自然科学基金资助项目(No.82471629 （）
No.82171583) （）
深圳市医疗卫生三名工程项目(No.SZSM202211010) （No.SZSM202211010）
深圳市医学重点学科建设经费资助项目(No.SZXK069) （No.SZXK069）
