Compared with the mild effects of the non-inducible manipulation of brain LepR signaling, our Agrp-Lepr KO model showed a robust disruption in various feeding and metabolism parameters, culminating in severe obesity, which was previously achieved by global genetic deletion or the CRISPR–Cas9 technique (Xu et al., 2018; van de Wall et al., 2008; Gonçalves et al., 2014; Egan et al., 2017). This evidence concerns the gene AGRP and obesity due to melanocortin 4 receptor deficiency.