El-Haschimi et al. [53] showed that, in diet-induced obesity (DIO) mice, a classical mouse model of leptin resistance and obesity, recombinant leptin completely failed to induce STAT3 activation in hypothalamic extracts, demonstrating severe leptin-resistant signaling in the hypothalamus of DIO mice. The gene discussed is STAT3; the disease is obesity due to melanocortin 4 receptor deficiency.