INS and obesity due to melanocortin 4 receptor deficiency: Although obesity may play a major role in the development of insulin resistance, recent studies suggest that ectopic lipid accumulation in insulin-targeting organs, such as the liver [1] and skeletal muscles [2], in an overnutrition state may also contribute to the pathology of insulin resistance via perturbation of inter-organ networks mediated by nutrients, hepatokines/myokines, and neuronal pathways [3].