INS and obesity due to melanocortin 4 receptor deficiency: In addition, TLR4−/− mice are protected against down-regulation of insulin signaling in skeletal muscle upon systemic lipid infusion [11], [12], and C3H/HeJ mice bearing a loss-of-function mutation in TLR4 do not develop diet-induced obesity or insulin-resistance in skeletal muscle [14], nor do they develop dietary hepatic steatosis [15].