In these regions, leptin signaling is mediated by the JAK2/Stat3 pathway, in which several negative regulators of JAK2, including SOCS3 and PTP1B, have been reported to promote obesity [20,21], supporting the notion that JAK2 inhibitory molecules increase risk for leptin resistance and obesity. Here, JAK2 is linked to obesity due to melanocortin 4 receptor deficiency.