INS and obesity due to melanocortin 4 receptor deficiency: The latter seems more plausible given that a direct action of leptin on its hypothalamic neuronal target is required to maintain normal glucose homeostasis data and insulin sensitivity [68, 69] and therefore the rising leptin level and insulin resistance in obesity lends plausibility to the conclusion that another fat derived molecule required for the leptin effect on glucose homeostasis may be downregulated in obesity for this paradoxical observation to hold.