However, no dogmas can be concluded since a pathogenetic involvement of SOCS3 has also been shown: in obesity, chronic JAK–STAT3 activation in the CNS by increased circulating leptin levels lead to the development of leptin resistance, whereas in the peripheral organs chronic IL-6-induced STAT3 activation impairs insulin action (157). The gene discussed is LEP; the disease is obesity due to melanocortin 4 receptor deficiency.