Despite the fact that the function of α-MSH and AgRP in circulation, especially in relation to energy balance, is still not elucidated, it seems that obesity-induced hyperleptinemia—by making hypothalamic resistance to function of these hormones and deregulation in hypothalamic expression of these neuropeptides—may contribute to positive energy balance and development of adiposity [59, 60]. This evidence concerns the gene AGRP and obesity due to melanocortin 4 receptor deficiency.