Abedi Azam, Foroutan Tahereh, Mohaghegh Shalmani Leila, Dargahi Leila
Department of Animal Biology, Faculty of Biological Sciences, Kharazmi University, Tehran, Iran.
Department of Animal Biology, Faculty of Biological Sciences, Kharazmi University, Tehran, Iran.
Mech Ageing Dev. 2023 Apr;211:111795. doi: 10.1016/j.mad.2023.111795. Epub 2023 Feb 23.
Peripheral metabolic disturbances are associated with a variety of clinical health consequences and may contribute to the development of neurocognitive disorders. This study investigates whether long-term high-fat diet (HFD) consumption changes the brain glucose metabolism and impairs memory performance in a sex-dependent manner. Male and female rats, after weaning, were fed HFD or normal chow diet (NCD) for 16 weeks. Behavioral tests for spatial memory and an 18 F-FDG-PET scan were performed. Also, the expression of brain insulin resistance markers and Alzheimer's pathology-related genes was assessed by qPCR. The Morris water maze and Y-maze results showed, respectively, that memory retrieval and spatial working memory were impaired only in HFD male rats compared to NCD controls. In addition, measuring whole brain 18 F-FDG uptake indicated a significant reduction in glucose metabolism in male but not female HFD rats. Analysis of 15 genes related to glucose metabolism and Alzheimer's pathology, in the hippocampus, showed that expression of GLUT3, IRS2, and IDE is significantly reduced in HFD male rats. Our results suggest that sex affects the HFD-induced dysregulation of brain glucose metabolism and cognitive performance.
外周代谢紊乱与多种临床健康后果相关，可能促成神经认知障碍的发展。本研究调查长期高脂饮食（HFD）的摄入是否会以性别依赖的方式改变大脑葡萄糖代谢并损害记忆表现。雄性和雌性大鼠在断奶后分别喂食HFD或正常饲料（NCD）16周。进行了空间记忆行为测试和18F-FDG-PET扫描。此外，通过qPCR评估大脑胰岛素抵抗标志物和阿尔茨海默病病理相关基因的表达。莫里斯水迷宫和Y迷宫结果分别显示，与NCD对照组相比，仅HFD雄性大鼠的记忆提取和空间工作记忆受损。此外，测量全脑18F-FDG摄取表明，雄性而非雌性HFD大鼠的葡萄糖代谢显著降低。对海马体中与葡萄糖代谢和阿尔茨海默病病理相关的15个基因进行分析，结果显示HFD雄性大鼠中GLUT3、IRS2和IDE的表达显著降低。我们的结果表明，性别会影响HFD诱导的大脑葡萄糖代谢失调和认知表现。
