Dodd et al. recently report that a combined action of leptin and insulin on POMC neurons promotes WAT browning and energy expenditure and prevents diet-induced obesity through protein tyrosine phosphatase 1B (PTP1B) and T cell protein tyrosine phosphatase (TCPTP) signaling as deletion of the phosphatases PTP1B and TCPTP enhanced insulin and leptin signaling in POMC neurons (80). Here, POMC is linked to obesity due to melanocortin 4 receptor deficiency.