Hotamisligil and colleagues showed early on there is a substantial increase in expression of the pro-inflammatory cytokine tumor necrosis factor (TNF)α in several rodent models of obesity and that neutralizing TNFα could improve insulin-sensitivity in these animals (Hotamisligil et al., 1993, 1995; Uysal et al., 1997). The gene discussed is TNF; the disease is obesity due to melanocortin 4 receptor deficiency.