Importantly, global knockout of JNK isoform-1 (JNK1), a ubiquitously expressed isoform, protects mice from developing diet-induced obesity (DIO)9, which supports a role for JNK, mediated in part by JNK1, in promoting high fat diet-induced obesity. This evidence concerns the gene MAPK8 and obesity due to melanocortin 4 receptor deficiency.