The first link between obesity, inflammation and insulin action came from a study developed by Hotamisligil et al. [13], which demonstrated that tumor necrosis factor (TNF)-α mRNA expression in the adipose tissue of obese animal (fa/fa rat and ob/ob mouse) was increased and that the neutralization of TNF-α improved insulin action on glucose uptake. This evidence concerns the gene INS and obesity due to melanocortin 4 receptor deficiency.