NFKB1 and obesity due to melanocortin 4 receptor deficiency: Obesity is associated with overproduction of multiple proinflammatory mediators that contribute to insulin resistance by activation of NF-κB.73, 74 Genetic or pharmacologic inhibition of this pathway with aspirin,75 adiponectin,76 thiazolidinediones77 or statins78 has been shown to ameliorate obesity-induced insulin resistance.9, 79, 80, 81 The hyperglycemia of diabetes, if unchecked, fosters further inflammation via oxidative damage.