Importantly, since these POMC-SOCS3 KO mice given a HFD still show an increase in body weight and hyperleptinemia compared to LFD mice (albeit both are attenuated compared to HFD control mice), it is clear that additional mechanisms (e.g. elevated LepRb and/or SOCS3 (and/or PTP1B and/or PTPN2) expression in other neurons (e.g. AgRP)) also play important roles in the development of leptin resistance and diet-induced obesity. The gene discussed is LEP; the disease is obesity due to melanocortin 4 receptor deficiency.