Although, the mechanism by which obesity can increase PD-1 expression has not been fully elucidated, increased levels of leptin secreted from adipose tissues has been suggested to boost cascade signaling indirectly through signal transduction and activator of transcription 3 (STAT3) which leads to upregulation of PD-1 receptors on T-cells (Figure 2). The gene discussed is LEP; the disease is obesity due to melanocortin 4 receptor deficiency.