It was elucidated that proinflammatory cytokines promote obesity-associated insulin resistance through activating inflammatory signaling pathways, including the stress-responsive c-Jun NH2-terminal kinase (JNK1/2) and AMP-activated protein kinase α2 (AMPKα2), inhibitor of κB kinase, and extracellular signal-regulated kinase 1/2 (ERK1/2) as well as MAPKp38, collectively causing inhibition of serine/threonine phosphorylation of the docking protein IRS-148–50. Here, MAPK3 is linked to obesity due to melanocortin 4 receptor deficiency.