SOCS3 and obesity due to melanocortin 4 receptor deficiency: In the hypothalamus, the expression of negative regulators such as the suppressors of cytokine signaling 3 (SOCS3), protein tyrosine phosphatase 1B (PTP1B), and T cell protein tyrosine phosphatase (TCPTP) increase in obesity, and, in turn, the hypothalamic–pituitary axis becomes resistant to leptin signaling.