Disease modeling using human induced pluripotent stem cells combined with the CRISPR/Cas9 technique may allow us to study and better understand abnormal leptin signaling in cardiomyocytes as well as in endothelial cells in vitro, which might cause obesity- and T2DM-associated cardio-metabolic remodeling processes. This evidence concerns the gene LEP and obesity due to melanocortin 4 receptor deficiency.