Impact of high-fat diet on antioxidant status, vascular wall thickening and cardiac function in adult female LDLR<sup>–/–</sup> mice

Background: Western diet, rich in saturated fatty acids and cholesterol, is associated with increased cardiovascular risk. We thus investigated in female mice the influence of this diet on plasma antioxidant status, vascular wall thickening and cardiac function. Methods and Results: Adult female C57BL/6J wild type (WT) and LDLR–/– mice were fed a normal diet (ND) or a high-fat diet (HFD) for 17 weeks. HFD in- duced an increase in plasma lipids and vitamin C (Vit C) levels in both groups but at a much higher level in LDLR–/– and a decrease in plasma ascorbyl free radi- cal levels to Vit C ratio (an endogenous oxidative stress index) in LDLR–/–. We only found a slight de- crease in circulating antioxidant status evaluated by the Oxygen Radical Absorbance Capacity (ORAC) assay in WT, but not in LDLR–/–. Echocardiography evidenced an increase in arterial wall thickness in aortic arch at atherosclerosis predilection sites in HFD LDLR–/– as compared to ND LDLR–/– and HFD WT. This result was confirmed by histology. Further- more, histological examination of aortic valves showed an increase in atherosclerotic lesions. Our study, us- ing echocardiography, show that chronic HFD does not induce any major modifications of systolic func- tion in the both mice groups. Conclusions: High-fat intake in mice causes serious disturbances in lipid plasma levels associated to variations of circulating antioxidant status due, at least in part, to an increase in Vit C. At this stage, atherosclerotic lesions, ob- served in aortic arch and valve, do not impair cardiac function in HFD-fed mice.