Institutes of Biomedical Sciences, School of Medicine, Jianghan University, Wuhan 430056, China.
Department of Pathology and Pathophysiology, School of Medicine, Jianghan University, Wuhan 430056, China.
Nutrients. 2023 Jan 3;15(1):250. doi: 10.3390/nu15010250.
High-fat diet (HFD) intake is commonly related to a substantial risk of cognitive impairment for senior citizens over 65 years of age, which constitutes a profound global health burden with several economic and social consequences. It is critical to investigate the effects of long-term HFD consumption on cognitive function and to inspect the potential underlying mechanisms. In the present study, 9-month-old male C57BL/6 mice were randomly assigned to either a normal diet (ND, 10 kcal% fat) or an HFD diet (60 kcal% fat) for 10 months. Then a series of behavioral tests, and histological and biochemistry examinations of the hippocampus and cortex proceeded. We found that long-term HFD-fed aged mice exhibited cognitive function decline in the object place recognition test (OPR). Compared with the ND group, the HFD-fed mice showed Tau hyperphosphorylation at ps214 in the hippocampus and at ps422 and ps396 in the cortex, which was accompanied by GSK-3β activation. The higher activated phenotype of microglia in the brain of the HFD group was typically evidenced by an increased average area of the cell body and reduced complexity of microglial processes. Immunoblotting showed that long-term HFD intake augmented the levels of inflammatory cytokines IL-6 in the hippocampus. These findings indicate that long-term HFD intake deteriorates cognitive dysfunctions, accompanied by Tau hyperphosphorylation, microglial activation, and inflammatory cytokine expression, and that the modifiable lifestyle factor contributes to the cognitive decline of senior citizens.
高脂肪饮食（HFD）摄入通常与 65 岁以上老年人认知障碍的风险显著增加有关，这给全球健康带来了严重负担，并带来了许多经济和社会后果。因此，研究长期 HFD 摄入对认知功能的影响，并研究潜在的潜在机制至关重要。在本研究中，9 个月大的雄性 C57BL/6 小鼠被随机分为正常饮食（ND，10 kcal%脂肪）或高脂肪饮食（HFD，60 kcal%脂肪）组，分别喂养 10 个月。然后进行了一系列行为测试以及海马体和皮质的组织学和生物化学检查。我们发现，长期 HFD 喂养的老年小鼠在物体位置识别测试（OPR）中表现出认知功能下降。与 ND 组相比，HFD 喂养的小鼠在海马体中 Tau 在 ps214 处发生过度磷酸化，在皮质中在 ps422 和 ps396 处发生过度磷酸化，同时 GSK-3β 被激活。HFD 组大脑中微胶质细胞的更高激活表型通常通过增加细胞体的平均面积和减少微胶质细胞过程的复杂性来证明。免疫印迹显示，长期 HFD 摄入增加了海马体中炎症细胞因子 IL-6 的水平。这些发现表明，长期 HFD 摄入可导致认知功能障碍恶化，伴随着 Tau 过度磷酸化、小胶质细胞激活和炎症细胞因子表达，可改变的生活方式因素可导致老年人认知能力下降。
