MAPK8 and obesity due to melanocortin 4 receptor deficiency: After over a decade of study of the physiological function of MKP-1 in the regulation of metabolic homeostasis in mice and more recently in humans, these data collectively point to the notion that chronic upregulation of MKP-1 in skeletal muscle is part of a stress response mediated by p38 MAPK and JNK activities and this may play an important contributing role in the development of insulin resistance, T2D and obesity.