Although these findings do not demonstrate precisely what secretory changes APP-overexpressing macrophage may be exhibiting in situ during diet-induced obesity, they do provide clear evidence that APP stimulated changes in macrophage phenotype are complex with alterations in both proinflammatory and anti-inflammatory secretion that will need to be further resolved in vivo in the diet-induced obesity model. This evidence concerns the gene APP and obesity due to melanocortin 4 receptor deficiency.