Resulting from the combination of three main factors – genetic disposition, large food intake and physical inactivity—obesity leads to an imbalance between the energy supply and expenditure, increasing free fatty acids in the blood and in turn reducing glucose utilization in muscle and fatty tissues, finally contributing to insulin resistance and an increase of insulin release, further raised by the resulting down-regulation of the insulin receptors. Here, INS is linked to obesity due to melanocortin 4 receptor deficiency.