Although TNFα is elevated in diabetic patient and animal model of diabetes (Yamakawa et al., 1995; Pereira et al., 2006a; Preciado-Puga et al., 2014), little was known about its role in cellular alteration, notably regarding the Ca2+ signaling pathway and gender specificity in animal model of diabetes linked to obesity. This evidence concerns the gene TNF and obesity due to melanocortin 4 receptor deficiency.