Our study demonstrated that loss of Tet2 in adipocytes led to the reduction of circulating leptin levels (Fig. 5a) and a marked increase in basal and leptin-induced p-STAT3 levels in the hypothalamus (Fig. 5c), accompanied by resistance to HFD-induced obesity (Fig. 4a). Here, TET2 is linked to obesity due to melanocortin 4 receptor deficiency.