In hypertrophic adipose tissue (a frequent characteristic of obesity), NF-κB and HIF-1α are capable of overregulating the expression of genes that encode proinflammatory cytokines, such as IL-6 and TNF-α which, in turn, have direct deleterious effects on the insulin cell signaling pathway [36]. Here, INS is linked to obesity due to melanocortin 4 receptor deficiency.