Potential link of high fat diet and mRNA expression of Alzheimer's disease-related genes in the enteric mucosa of a rat model of Alzheimer's disease

Background High-fat diet (HFD) consumption is linked to Alzheimer's disease (AD). Identifying changes in the mRNA expression due to the ingestion of HFD in the intestine—often called the second brain due to its dense enteric neurons—could offer insights into AD development and progression. Objective This study assesses whether the introduction of HFD at adult-age influence expression of AD-related genes in the intestines of Wild-type (WT) or the amyloid precursor protein/presenilin1 (APP/PS1)-overexpressing Transgenic (TG) rats. Methods Twelve-month-old WT and TG rats (male and female) were fed a control diet (CD; 8% energy from fat), or HFD (45% energy from fat) for six months. Ileal tissues were assessed for the mRNA expression of genes responsible for development/progression of AD. Results The WT HFD-fed rats (compared to CD-fed rats) showed increased mRNA expression of genes involved in the development of AD. In contrast, the TG HFD-fed female group, showed a higher number of upregulated genes compared to their respective CD-fed TG group. In TG HFD-fed rats there was higher mRNA expression of genes crucial for synaptic transmission such as Brain-derived neurotrophic factor in females and Choline acetyltransferase in males. Expression of Plasminogen was higher in HFD-fed TG female rats and HFD-fed WT male rats. Overall, the HFD-fed WT male showed mRNA expression of genes involved in the development of AD. However, HFD-fed TG females were more vulnerable for the progression of AD. It is likely that the enteric Plasminogen plays a major role in gut-brain axis for the development of AD in WT male, and progression of AD in TG female during the consumption of HFD. Conclusions The consumption of HFD perturbed the expression of enteric genes known to be involved in amyloid-β generation, clearance, and degradation, in a sex-dependent manner.