Objectives To provide evidence that rosuvastatin could improve insulin-resistance and inhibit atherogenesis by modulating insulin signalling, and whether this effect beyond its plasma cholesterol-lowering effect.

Methods Thirty-two 6-week-old low-density lipoprotein receptor deficient (LDLR- /-) mice were randomised into four groups (n = 8 in each group): Normal control group (NC); High fat and high fructose diet group (HFF); HFF plus rosuvastatin group (HFFR); HFFR plus mevalonic acid group (HFFRMA). After 12 weeks, we measured the fasting blood sugar (FBS), fasting insulin (FINS) and total cholesterol (TC); the morphological concentrations of the aorta artery and aorta sinus; the expression of insulin receptor substrate 2 (IRS-2), phosphorylated insulin receptor substrate 2 (P-IRS-2), protein kinase B (AKT, also known as PKB) and phosphorylated protein kinase B (P-AKT) in liver.

Results Compared with other groups, FBS and FINS increased significantly in HFF group. Furthermore, HFF group had an increase in the morphological concentrations of the aorta artery and aorta sinus, but there was a significant decrease in HFFRMA group and HFFR group. Moreover, there was a high expression of IRS-2, P- IRS-2, AKT and P-AKT in HFFRMA group and HFFR group, but a low expression in HFF group. And there is no significant difference regarding to each afore-mentioned index in HFFR group and HFFRMA group.

Conclusions Our data show that rosuvastatin could improve insulin-resistance and inhibit atherogenesis in HFF-fed mice by partially reversing the decrease in the insulin stimulated IRS-2/PI3-K/AKT pathway in liver, and this effect is independent of its cholesterol-lowering effect.