High-fat diet-induced obesity exacerbates kainic acid-induced hippocampal cell death

Obesity has deleterious effects on the brain, and metabolic dysfunction may exacerbate the outcomes of seizures and brain injuries. However, it is unclear whether obesity affects excitotoxicity-induced neuronal cell death. The purpose of this study was to investigate the effects of a high-fat diet (HFD) on neuroinflammation and oxidative stress in the hippocampus of kainic acid (KA)-treated mice. Mice were fed with a HFD or normal diet for 8 weeks and then received a systemic injection of KA. HFD-fed mice showed hypercholesterolemia, insulin resistance, and hepatic steatosis. HFD-fed mice showed greater susceptibility to KA-induced seizures, an increased number of terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cells, neuroinflammation, and oxidative stress. Furthermore, we found that KA treatment increased HFD-induced calpain1, nuclear factor E2-related factor 2, and heme oxygenase-1 expression in the hippocampus. These findings imply that complex mechanisms affected by obesity-induced systemic inflammation, neuroinflammation, ER stress, calcium overload, and oxidative stress may contribute to neuronal death after brain injury.