Abstract

The atheroprotective potential of n-3 alpha-linolenic acid (ALA) has not yet been fully determined, even in murine models of atherosclerosis. We tested whether ALA-derived, n-3 long chain polyunsaturated fatty acids (LCPUFA) could offer atheroprotection in a dose-dependent manner. Apolipoprotein B (ApoB)100/100LDLr-/- mice were fed with diets containing two levels of ALA from flaxseed oil for 16 weeks. Fish oil- and cis-monounsaturated-fat-enriched diets were used as positive and negative controls, respectively. The mice fed cis-monounsaturated fat and ALA-enriched diets exhibited equivalent plasma total cholesterol (TPC) and LDL-cholesterol (LDL-c) levels; only mice fed the fish-oil diet had lower TPC and LDL-c concentrations. Plasma LDL-CE fatty acid composition analysis showed that ALA-enriched diets lowered the percentage of atherogenic cholesteryl oleate compared with cis-monounsaturated-fat diet (44% versus 55.6%) but not as efficiently as the fish-oil diet (32.4%). Although both ALA and fish-oil diets equally enriched hepatic phospholipids with eicosapentaenoic acid (EPA) and ALA-enriched diets lowered hepatic cholesteryl ester (CE) levels compared with cis-monounsaturated-fat diet, only fish oil strongly protected from atherosclerosis. These outcomes indicate that dietary n-3 LCPUFA from fish oil and n-3 LCPUFA (mostly EPA) synthesized endogenously from ALA were not equally atheroprotective in these mice.

Highlights

  • The atheroprotective potential of n-3 ␣-linolenic acid (ALA) has not yet been fully determined, even in murine models of atherosclerosis

  • Cis-monounsaturated fat was selected as the atherogenic comparator fat because in several different animal models and experimental conditions it consistently promoted the highest aortic cholesteryl ester deposition which is the chemical endpoint used to quantify the extent of atherosclerosis in this study [15, 16, 20, 21]

  • This report provides original, clear documentation of the distinct effects of n-3 long chain polyunsaturated fatty acids (LCPUFA) derived from ALA versus dietary eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) from fish oil on atherosclerotic lesion formation in mice

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Summary

Introduction

The atheroprotective potential of n-3 ␣-linolenic acid (ALA) has not yet been fully determined, even in murine models of atherosclerosis. Plasma LDL-CE fatty acid composition analysis showed that ALA-enriched diets lowered the percentage of atherogenic cholesteryl oleate compared with cis-monounsaturated-fat diet (44% versus 55.6%) but not as efficiently as the fish-oil diet (32.4%). Both ALA and fish-oil diets enriched hepatic phospholipids with eicosapentaenoic acid (EPA) and ALA-enriched diets lowered hepatic cholesteryl ester (CE) levels compared with cis-monounsaturated-fat diet, only fish oil strongly protected from atherosclerosis These outcomes indicate that dietary n-3 LCPUFA from fish oil and n-3 LCPUFA (mostly EPA) synthesized endogenously from ALA were not atheroprotective in these mice.— Degirolamo, C., K. Oily fish is the richest dietary source of EPA and DHA, its consumption in most Western countries is low and inadequate to provide the recommended daily intake (250–500 mg of EPA and DHA) [3] Vegetable oils, such as flaxseed, soybean, and canola oil, and nuts, such as English walnuts, that are enriched in ␣-linolenic acid (ALA) can serve as alternative sources of EPA and DHA.

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