Since all three models of obesity/HFD-associated increased inflammation in the skin present defective M2-like macrophage induction that coincides with the overexpression of S100A8 and S100A9 in the inflamed skin tissue, and since macrophages express receptors for both such as TLR4 and RAGE, we asked whether S100A8 and S100A9 impair M2-like macrophage differentiation. Here, S100A9 is linked to obesity due to melanocortin 4 receptor deficiency.