Hippocampal neural cell loss in high-fat diet-induced obese rats-exploring the protein networks, ultrastructure, biochemical and bioinformatical markers

Objective: Obesity, which has become one of the main health problems, results from irregular and unhealthy nutrition. In particular, an increase in the intake of high-fat foods leads to obesity and associated disorders. It is noteworthy to specify that obese individuals have memory problems. This study aims to examine the effects of high-fat diet on hippocampus, with stereological, histopathological methods and STRING bioinformatic tool. Methods: Female Adult Sprague Dawley rats (n = 20) were equally divided into control (CONT) and high-fat diet (HFD) groups. The control group was given standard rat pellet feed, while the high-fat diet group was fed with a 40 % fat content for 2 months. Following the feeding program, rats were sacrificed. The collected blood samples were analyzed biochemically to determine the level of oxidative stress while performing a stereological and histopathological examination of the brain tissues. Functional protein-protein networks for BDNF, C-Fos, CAT, LPO, SOD and MPO by gene ontology (GO) enrichment analysis were evaluated. Findings: The number of neurons decreased in the HFD group compared to the CONT group. Damage to the histological structure of the hippocampus region; such as degenerate neurons, damaged mitochondria and extended cisterns of the endoplasmic reticulum was observed. Although C-Fos level and oxidative stress parameters increased in HFD group, BDNF level decreased. While BDNF and C-Fos were observed in pathways related to neuron death, oxidative stress and memory, BDNF was pronounced in the mitochondria, and C-Fos in the endoplasmic reticulum. Discussion: This study shows that changes in both BDNF and C-Fos levels in obesity due to high-fat diet increase oxidative stress and cause neuron damage in the hippocampus.