In addition to the accumulation of bone marrow-derived macrophages, there is also a shift from anti-inflammatory “alternatively activated” (CD11c-CD206+) M2 macrophages to proinflammatory “classically activated” (CD11c+CD206-) M1 macrophages (Sun et al., 2011; Glass and Olefsky, 2012), which in advanced obesity aggregate into crown-like structures (CLS) surrounding necrotic adipocytes. This evidence concerns the gene ITGAX and obesity due to melanocortin 4 receptor deficiency.