高碳水化合物饮食通过PI3K/Akt/GSK-3β信号通路诱导db/db小鼠认知障碍并增加淀粉样蛋白负荷和tau蛋白磷酸化。

A High-Carbohydrate Diet Induces Cognitive Impairment and Promotes Amyloid Burden and Tau Phosphorylation via PI3K/Akt/GSK-3β Pathway in db/db Mice.

作者信息

Xu Jialu, Xie Lei, Yin Jiaxin, Shi Xiaoli, Dong Kun, Tao Jing, Xu Weijie, Ma Delin, Zhang Shujun, Chen Juan, Yang Yan

机构信息

Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.

Branch of National Clinical Research Center for Metabolic Diseases, Wuhan 430030, China.

出版信息

Biomedicines. 2024 Jul 31;12(8):1701. doi: 10.3390/biomedicines12081701.

BACKGROUND

Cognitive impairment is a prevalent complication of type 2 diabetes, influenced significantly by various dietary patterns. High-carbohydrate diets (HCDs) are commonly consumed nowadays; however, the specific impact of HCDs on cognitive function in diabetes remains unclear.

METHODS

The objective of this study was to investigate whether an HCD has effects on cognition in diabetes. Eight-week-old diabetic (db/db) mice and wild-type (WT) mice underwent a twelve-week dietary intervention, including a normal diet (ND), an HCD, or a high-fat diet (HFD). Following this, behavioral tests were conducted, and related hippocampal pathology was evaluated.

RESULTS

Our results demonstrated that an HCD exacerbated cognitive decline in db/db mice compared to an ND. Additionally, an HCD increased amyloid-β burden and expression of β-site APP cleaving enzyme-1. An HCD was also found to promote the phosphorylation of tau protein via the PI3K/Akt/GSK-3β pathway. Furthermore, an HCD markedly induced neuroinflammation and increased the quantity of microglia and astrocytes. However, these damages induced by an HCD were less severe than those caused by an HFD.

CONCLUSIONS

Collectively, our findings indicate that a high intake of carbohydrates can have an adverse impact on cognitive function in diabetes.

背景

认知障碍是2型糖尿病常见的并发症，受多种饮食模式的显著影响。如今高碳水化合物饮食（HCD）很常见；然而，HCD对糖尿病患者认知功能的具体影响仍不清楚。

方法

本研究的目的是调查HCD是否对糖尿病患者的认知有影响。8周龄的糖尿病（db/db）小鼠和野生型（WT）小鼠接受了为期12周的饮食干预，包括正常饮食（ND）、HCD或高脂饮食（HFD）。之后，进行行为测试，并评估相关的海马病理学。

结果

我们的结果表明，与ND相比，HCD加剧了db/db小鼠的认知衰退。此外，HCD增加了淀粉样蛋白-β负荷和β-位点APP裂解酶-1的表达。还发现HCD通过PI3K/Akt/GSK-3β途径促进tau蛋白的磷酸化。此外，HCD明显诱导神经炎症，并增加小胶质细胞和星形胶质细胞的数量。然而，HCD诱导的这些损伤不如HFD造成的损伤严重。