All together our in vitro and in vivo data demonstrate that sustained overexpression of S100A9 in skin inflammation in obesity is mediated by SFA that initiate and drive a positive feedback loop between skin cells and the dermal macrophage compartment via the induction of an inflammasome-dependent IL-1β release (Figure 8). The gene discussed is S100A9; the disease is obesity due to melanocortin 4 receptor deficiency.