Chronic activatated JAK-STAT3 pathway has been summarized to contribute to obesity [31] and peripheral insulin resistance[32], [33] as well as leptin resistance[33].On the other hand, TNF-α is one of the best described causative factors in obesity-associated insulin resistance and the pathogenesis of T2D [34]. Here, TNF is linked to obesity due to melanocortin 4 receptor deficiency.