MAPK8 and obesity due to melanocortin 4 receptor deficiency: As was shown from studies in high-fat diet fed mice, in obesity, important mediators in the observed leptin resistance in AgRP neurons are JNK, NF-kB, suppressor of cytokine signaling 3 (SOSC3), protein tyrosine phosphatase 1B (PTP1B, also known as polypyrimidine tract binding protein 1), and PKC [127,128].