Here, we show that endoplasmic reticulum (ER) stress was activated in the hippocampus and processes of Dcx-expressing immature neurons were shortened, coexpressing CHOP in APP23 AD model mice with high-fat diet-induced long-term obesity and in aged Leprdb/db (db/db) mice. This evidence concerns the gene DDIT3 and obesity due to melanocortin 4 receptor deficiency.