Supporting this, previous results suggest that the leptin-inhibitory action is independent of pSTAT3 signaling22 and, importantly, that antagonism of leptin action effectively increases feeding and obesity in DIO mice, arguing for intact leptin action in DIO states.44,45 Interestingly, one previous study suggests that HFD feeding negates the response of ob/ob mice to leptin treatment in reducing body weight, which is associated with an intact p-STAT3 response,46 suggesting the existence of additional neuron groups in mediating leptin resistance. This evidence concerns the gene STAT3 and obesity due to melanocortin 4 receptor deficiency.