Knockdown of myeloid differentiation primary response gene 88 (MYD88) (Supplementary Fig. 17), an adaptor protein for TLR4, improved the insulin resistance in LKO mice (Fig. 7e,f), and overexpression of PRSS8 in the liver did not decrease blood glucose levels during the GTT and PTT in systemic TLR4 KO mice (Supplementary Fig. 18). The gene discussed is PRSS8; the disease is Insulin resistance.