NOS2 and obesity due to melanocortin 4 receptor deficiency: ER stress has been shown to suppress M2 polarization of macrophages in obesity [32]. M2 macrophages usually generate anti-inflammatory cytokines IL-10 and IL-1 decoy receptors. M2 polarization results in increased production of “arginase”, an enzyme which blocks inducible nitric oxide synthase (iNOS) activity and competes with the arginine, a substrate required for nitric oxide (NO) production [33].