It is tempting to speculate that the age- and obesity-related increase in p16INK4a and P53 levels in AT [49,52,53,64], not only facilitates the recruitment of macrophages in AT, but also hampers macrophage M2 polarization and contributes to T2D risk. This evidence concerns the gene CDKN2A and obesity due to melanocortin 4 receptor deficiency.