High-Fat Diet Alleviates Neuroinflammation and Metabolic Disorders of APP/PS1 Mice and the Intervention With Chinese Medicine

• Main Authors: Xiaorui Fan, Bin Liu, Junyi Zhou, Xinru Gu, Yanyan Zhou, Yifei Yang, Feifei Guo, Xiaolu Wei, Hongjie Wang, Nan Si, Jian Yang, Baolin Bian, Haiyu Zhao
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2021-06-01
• Series: Frontiers in Aging Neuroscience
• Subjects: Alzheimer's disease; high fat diet; neuroinflammation; metabolism; Huanglian Jiedu decoction; gut microbiota
• Online Access: https://www.frontiersin.org/articles/10.3389/fnagi.2021.658376/full

Alzheimer's disease (AD) is a progressive neurodegenerative disease caused by the complex interaction of multiple mechanisms. Recent studies examining the effect of high-fat diet (HFD) on the AD phenotype have demonstrated a significant influence on both inflammation and cognition. However, different studies on the effect of high-fat diet on AD pathology have reported conflicting conclusions. To explore the involvement of HFD in AD, we investigated phenotypic and metabolic changes in an AD mouse model in response to HFD. The results indicated there was no significant effect on Aβ levels or contextual memory due to HFD treatment. Of note, HFD did moderate neuroinflammation, despite spurring inflammation and increasing cholesterol levels in the periphery. In addition, diet affected gut microbiota symbiosis, altering the production of bacterial metabolites. HFD created a favorable microenvironment for bile acid alteration and arachidonic acid metabolism in APP/PS1 mice, which may be related to the observed improvement in LXR/PPAR expression. Our previous research demonstrated that Huanglian Jiedu decoction (HLJDD) significantly ameliorated impaired learning and memory. Furthermore, HLJDD may globally suppress inflammation and lipid accumulation to relieve cognitive impairment after HFD intervention. It was difficult to define the effect of HFD on AD progression because the results were influenced by confounding factors and biases. Although there was still obvious damage in AD mice treated with HFD, there was no deterioration and there was even a slight remission of neuroinflammation. Moreover, HLJDD represents a potential AD drug based on its anti-inflammatory and lipid-lowering effects.