The result that over-expression of LepRb in POMC neurons increases body weight in HFD mice is initially surprising, considering the well known anti-obesity effect of the leptin-LepRb system and our recent report showing that expression of LepRb in POMC neurons of Leprdb/db mice reduces body weight [16]. The gene discussed is POMC; the disease is obesity due to melanocortin 4 receptor deficiency.