AKT1 and Insulin resistance: In line with the insulin resistance shown in Fig 1E, IRS-1/Akt pathway in primary hepatocytes isolated from HFD-fed mice was substantially decreased as compared with the control group: there was a marked decrease in total IRS-1 (24% decline, p < 0.01) as well as the phosphorylated IRS-1 at Tyr608 (60.2% decline, p < 0.01) in mice fed with HFD compared with those on a control diet (Fig 2A), whereas there was a 120.3% increase (p < 0.05) in the phosphorylated IRS-1 at Ser307.