After three days of high-fat feeding with hepatic fat accumulation and hepatic insulin resistance in the absence of significant peripheral fat accumulation or peripheral insulin resistance, hepatic insulin resistance could be attributed to impaired insulin-stimulated Irs1 and Irs2 tyrosine phosphorylation, associated with activation of PKC-epsilon (PKCε) and JNK1 [158]. The gene discussed is IRS2; the disease is Insulin resistance.