This conundrum was resolved in 2003, with the publication in this journal of two seminal papers showing that the macrophage content of adipose tissue in mice goes up dramatically in both diet-induced and genetic obesity and that these proinflammatory cells are the source of TNF-α and many other cytokines (5, 6) (Figure 1). Here, TNF is linked to obesity due to melanocortin 4 receptor deficiency.