In fact, obesity and IR have intracellular mechanisms linked to macrophage inflammation in WAT; for example, 4 weeks on a high fat diet (HFD) seem to be enough to induce glucose intolerance and impaired insulin signaling, as evidenced by reducing insulin-stimulated Akt phosphorylation levels, that correlate with an increase in macrophage infiltration and genes related to the M1-like phenotype (CD11c+) (Macpherson et al., 2015). This evidence concerns the gene INS and obesity due to melanocortin 4 receptor deficiency.