IRS1 and obesity due to melanocortin 4 receptor deficiency: In the chronic peripheral inflammatory process in obesity and diabetes, the production of inflammatory cytokines can lead to serine phosphorylation of insulin receptor substrate-1 (IRS-1), which can inhibit the downstream signaling pathways like kappa B kinase (IKK), c-Jun N-terminal kinase (JNK), and extracellular signal regulated kinase 2 (ERK2).