Recent studies have shown that obesity leads to a proinflammatory and metabolically activated adipose tissue macrophage phenotype (MMe), which is mechanistically and functionally distinct from the classic proinflammatory M1 phenotype and driven in part by saturated fatty acids (such as palmitic acid) released by insulin-resistant adipocytes (12–14). Here, INS is linked to obesity due to melanocortin 4 receptor deficiency.