Abstract

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 induced 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 radical levels to Vit C ratio (an endogenous oxidative stress index) in LDLR–/–. We only found a slight decrease 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, using echocardiography, show that chronic HFD does not induce any major modifications of systolic function 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, observed in aortic arch and valve, do not impair cardiac function in HFD-fed mice.

Highlights

  • Western type high-fat diet (HFD), typically rich in saturated fatty acids and cholesterol, is associated with increased cardiovascular risk due, in part, to an abnormal increase in plasma cholesterol [1]

  • The aim of the present study was to evaluate in adult female C57BL/6J strains, in which LDLR was present or deleted, the influence of a 17-week HFD on plasma antioxidant status and on vascular wall thickening and cardiac function using high sensitivity echocardiography that proved to be an excellent tool for this purpose [10,13,14]

  • HFD did not influence this value in wild type (WT) mice, while in LDLR–/– mice, Heart rate (HR) was much higher than in all the other groups: compared with normal diet (ND) group (p = 0.019) or with HFD WT mice (p = 0.002)

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Summary

Introduction

Western type high-fat diet (HFD), typically rich in saturated fatty acids and cholesterol, is associated with increased cardiovascular risk due, in part, to an abnormal increase in plasma cholesterol [1]. We investigated in female mice the influence of this diet on plasma antioxidant status, vascular wall thickening and cardiac function. 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 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, observed in aortic arch and valve, do not impair cardiac function in HFD-fed mice

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