Figure 1. Chronic JAK-STAT3-SOCS3 signaling in obesity. Obesity increases circulating levels of leptin and IL-6 that in turn chronically activate intracellular JAK-STAT3 signaling. While Leptin (Lep) acts predominantly in the central nervous system, IL-6 has been reported to mainly function in peripheral organs, though both factors can also act vice versa. Chronic JAK-STAT3 signaling induced by leptin and IL-6 lead to the increased expression of the negative regulator SOCS3. SOCS3 in turn not only negatively regulates leptin and IL-6 signaling but also impairs insulin (INS) action eventually leading to obesity and insulin resistance.