In an effort to investigate the mechanisms of APOE promoted diet-induced obesity, in a recent study, we employed four different mouse models: Apoe-/-, Apoe3brain, Apoe3knock-in, and apoe-/- infected with an adenoassociated virus expressing APOE3 (AAV-E3)[57]. This evidence concerns the gene APOE and obesity due to melanocortin 4 receptor deficiency.