Of the multiple signaling pathways involved in obesity, the mitogen-activated protein kinase (MAPK) signaling members, extracellular signal-regulated kinase 1/2 (ERK1/2) and c-Jun N-terminal kinase (JNK), promote obesity by enhancing inflammation, insulin resistance, and adipogenesis. Here, MAPK3 is linked to obesity due to melanocortin 4 receptor deficiency.