In this context, it is well established that alterations in the integrity of the MAMs due to changes in the expression of proteins that conform or stabilize the IP3R-Grp75-VDAC complex induced by conditions of obesity, T2D, HFD, high-sucrose diet, and genetic modification have been associated with IR development (Arruda et al., 2014; Tubbs et al., 2014, 2018; Thoudam et al., 2019). This evidence concerns the gene ITPR1 and obesity due to melanocortin 4 receptor deficiency.