However, due to a feedback mechanism regulated by cytokine signalling 3 (SOCS3) and protein tyrosine phosphatase 1B (PTP1B), persistent leptin stimulation in obesity can lead to impaired leptin signalling and subsequent inability to mediate its anorexigenic effects, a state referred as ‘leptin resistance’ [76]. This evidence concerns the gene PTPN1 and obesity due to melanocortin 4 receptor deficiency.