Chronic inflammation in obesity activates multiple intracellular pathways that impair insulin signaling, notably via the activation of kinases (JNK, IKKβ, ERK1/2, p38 MAPK) which mediate the serine phosphorylation of insulin receptor substrates and disrupt the phosphoinositide 3-kinase (PI3K)/Akt cascade, essential for glucose uptake [88]. The gene discussed is INS; the disease is obesity due to melanocortin 4 receptor deficiency.