INSR and Hyperinsulinemia: 2022; Wang et al. 2022). High‐fat diet (HFD)‐induced T2DM mouse models exhibit hyperglycemia, impaired glucose tolerance, hyperinsulinemia, hyperleptinemia, and hippocampal IR, particularly the downregulation of insulin receptor expression in the brain (J. M. Kim et al. 2020). Therefore, HFD‐induced obese mice are usually used to study the pathophysiological mechanisms linking IR and cognitive dysfunction (de Paula et al. 2021).