Research Paper Volume 13, Issue 1 pp 1236—1250
High-fat diet induced discrepant peripheral and central nervous systems insulin resistance in APPswe/PS1dE9 and wild-type C57BL/6J mice
- 1 School of Public Health, Capital Medical University, Beijing 100069, P.R. China
Received: May 6, 2020 Accepted: July 21, 2020 Published: December 3, 2020https://doi.org/10.18632/aging.202262
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Copyright: © 2020 Guo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
This study was designed to examine whether AD pathological phenotype in APPswe/PS1dE9 (APP/PS1) mice exposed to continuous high-fat diet predispose these murine models to metabolic dysfunction and neuropathological impairments. One-month old male APP/PS1 and C57BL/6J mice were provided with 60% high-fat diet for 6.5 months. After dietary intervention, metabolic phenotyping, cognitive behaviors, AD-related brain pathological changes and insulin signaling were compared. high fat diet induced hyperglycemia, hypercholesterolemia, and aggravated inflammatory stress in both APP/PS1 and C57BL/6J mice. Compared with C57BL/6J control mice, APP/PS1 mice showed lower glucose transporter protein expression in liver, muscle, and brain. High-fat diet caused a decrease of glucose transporter protein expression in muscle and liver but increased cortical glucose transporter protein expression in APP/PS1 mice. High-fat diet-fed APP/PS1 mice demonstrated decreased cognitive function, as well as elevated cortical soluble amyloid-β levels and APP protein expression. Decrease in cortical IR, p-IR protein expression and p-GSK3β/GSK3β ratio were observed in high-fat diet-fed APP/PS1 mice. High-fat diet caused discrepant peripheral and central nervous system metabolic phenotype in APP/PS1 and C57BL/6J mice. AD pathological phenotype might accelerate metabolic changes and cognitive impairment in APP/PS1 mice treated with HFD.