(1) A decrease in IRS-2-mediated signal transduction was accompanied by increased SREBP-1c associated with insulin resistance.26 Furthermore, when mice on a high-fat diet were treated with ezetimibe, a selective inhibitor of intestinal cholesterol absorption, down-regulation of hepatic SREBP-1c and reversed insulin resistance (IR) was a consequence, which was associated with increased pY-IRS-2 and pS-AKT.27 Similarly, we observed increased SREBP-1c mRNA and protein level in S5KO and DKO livers as well as impaired IR signal transduction. The gene discussed is IRS2; the disease is Insulin resistance.