Recent evidence has demonstrated how the hypertrophic adipocyte causes very significant functional alterations in adipose tissue, with a consequent increase in the expression and secretion of adipokines with pro-inflammatory action, able to cause a systemic state of low-grade chronic inflammation, to worsen insulin sensitivity, and to contribute to the development of metabolic and cardiovascular complications associated with obesity [21]. Here, INS is linked to obesity due to melanocortin 4 receptor deficiency.