Consistent with the demonstration that obesity is associated with reversible PTP oxidation in the liver44, our study revealed that PTP1B was reversibly oxidized in response to insulin and leptin administration to animals fed a chow diet and that the levels of PTP1B-OX were elevated in the high fat diet-fed mouse model of obesity (Fig. 8a, b). This evidence concerns the gene LEP and obesity due to melanocortin 4 receptor deficiency.