TNF and obesity due to melanocortin 4 receptor deficiency: Since Hotamisligil and colleagues first showed that pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-α) was able to induce insulin resistance in four different rodent models of obesity and diabetes8, further inflammatory markers and mediators including C-reactive protein (CRP) and interleukin-6 (IL-6) were reported to be closely associated with T2DM9, 10.