2023 FDA Science Forum
Potential Link of High Fat Diet on the Expression of Alzheimer’s Disease Related Genes in the Ileal Mucosa of Alzheimer’s Disease Model of Rats
- Authors:
- Center:
-
Contributing OfficeNational Center for Toxicological Research
Abstract
A high-fat diet (HFD) is shown to have a profound effect on the gut and brain, and its consumption is linked to dementia accelerating Alzheimer's disease (AD) pathology. The aim of this study is to assess if HFD has any impact on the expression of AD related genes in the ileal mucosa of the gastrointestinal tract (GIT) and its potential links to the development of AD, using the RT-qPCR gene expression method in both wild-type (WT) and APP/PS1 overexpressed AD rat model. Our findings show that HFD significantly increased the mRNA expression of AD related key genes in the ileal tissue. Out of a total of 84 AD related genes, the metabolic consequences of HFD contributed to 52.4% of altered gene expression both WT and AD rats. Among them, WT rats had a higher number of genes expressed (88.6%) than in AD rats (36.4%).
The male rats showed significantly lower (9.09%) expression of those genes in the AD model than in WT (70.5%). Likewise, female rats also showed a similar pattern of lower gene expression in the AD model (32%) than in WT (52.3%). In female WT rats, expression of apoptotic genes such App (amyloid beta precursor protein) and EP300 (E1A binding protein p300) was markedly increased due to HFD. Additionally, in the HFD fed AD rats there was overexpression of genes like Bdnf (Brain derived neurotrophic factor) in females and Chat (choline acetyltransferase) in males, which are crucial for synaptic transmission. Earlier it was shown that the mucosal BDNF is in close proximity to the sensory nerve terminals; similarly, Chat is present in the cholinergic neurons in central and peripheral nervous system.
The higher percent of AD related genes expressed in WT on a HFD suggests that long-term consumption of HFD may have an impact on the expression of key neurotransmitters. The findings also show that the females are relatively more vulnerable to developing AD while consuming HFD. Studies are ongoing to correlate these gene expression patterns with the localization in the intestinal mucosa and abundance of microbiota in the GIT. This study will aid in the development of novel therapeutics for the prevention of AD.
