Given the elevated oxidative stress levels and the abnormal lipid metabolism, previously reported in PON2-deficient mice [2,112], Bourquard et al. hypothesized atherosclerosis as accompanied by impaired hepatic insulin signaling and showed PON2 deficiency as associated with inhibitory insulin-mediated phosphorylation of hepatic insulin receptor substrate-1 (IRS-1) [107]. Here, IRS1 is linked to atherosclerosis.