Elsevier

Atherosclerosis

Volume 220, Issue 1, January 2012, Pages 118-121
Atherosclerosis

Echium oil reduces atherosclerosis in apoB100-only LDLrKO mice

https://doi.org/10.1016/j.atherosclerosis.2011.10.025Get rights and content

Abstract

Introduction

The anti-atherogenic and hypotriglyceridemic properties of fish oil are attributed to its enrichment in eicosapentaenoic acid (EPA; 20:5, n-3) and docosahexaenoic acid (DHA; 22:6, n-3). Echium oil contains stearidonic acid (SDA; 18:4, n-3), which is metabolized to EPA in humans and mice, resulting in decreased plasma triglycerides.

Objective

We used apoB100 only, LDLrKO mice to investigate whether echium oil reduces atherosclerosis.

Methods

Mice were fed palm, echium, or fish oil-containing diets for 16 weeks and plasma lipids, lipoproteins, and atherosclerosis were measured.

Results

Compared to palm oil, echium oil feeding resulted in significantly less plasma triglyceride and cholesterol levels, and atherosclerosis, comparable to that of fish oil.

Conclusion

This is the first report that echium oil is anti-atherogenic, suggesting that it may be a botanical alternative to fish oil for atheroprotection.

Introduction

Dietary intervention is often the initial approach to reduce risk factors that contribute to cardiovascular heart disease, which is the leading cause of morbidity and mortality in Westernized societies [1]. Dietary consumption of long-chain n-3 PUFAs, such as those found in fatty fish or fish oil (FO) supplements, reduce inflammation, endothelial activation, and platelet activation, resulting in decreased cardiovascular disease [2]. The atheroprotective component of FO is attributed to two long-chain n-3 polyunsaturated fatty acids (PUFAs), eicosapentaenoic acid (EPA; 20:5 n-3) and docosahexaenoic acid (DHA; 22:6 n-3). Nonetheless, fatty fish and FO consumption in the United States remains low [2], [3]. The North American diet is rich in fatty acids that are pro-inflammatory and pro-atherogenic; 90% of the n-3 PUFAs consumed are in the form of alpha linolenic acid (ALA; 18:3 n-3) [3]. However, ALA is not atheroprotective because it requires Δ6-desaturase for conversion to EPA and DHA and this conversion is very inefficient (∼4–16%) in humans and rodents [4], [5]. Therefore, an alternative strategy is needed to compensate for the lack of EPA and DHA in the diet.

One approach is to enrich the diet with a fatty acid-containing oil that can be converted to EPA in vivo. Echium oil (EO), derived from the seeds of Echium plantagineum, contains 12–14% of total fatty acids as stearidonic acid (SDA; 18:4 n-3), the immediate product of ALA Δ6-desaturation. We have previously shown that SDA in EO is converted to EPA in plasma and liver lipids of a mouse model of atherosclerosis and hypertriglyceridemia, the apoB100 only LDL receptor knockout (B100 only, LDLrKO) mouse. EO, relative to a palm oil (PO) control diet, also reduced total plasma cholesterol (TPC) and triglyceride (TG) concentrations in B100 only, LDLrKO mice [6]. Similar enrichment of lipid fractions with EPA and reductions in plasma TG concentrations were observed in human subjects supplemented with EO [7]. These results established EO as a viable botanical alternative to FO for reducing plasma TG concentrations. However, whether EO is also atheroprotective is unknown.

The purpose of the present study was to determine whether EO consumption confers atheroprotection, and, if so, to what extent compared to that of FO. B100 only, LDLrKO mice were used for this study because they are a well-established mouse model for determining the effect of dietary fat saturation on atherosclerosis [8].

Section snippets

Animals and diets

Male apoB100-only LDLrKO mice in the C57BL/6 background (>99%) were housed in a specific pathogen-free facility at Wake Forest School of Medicine in accordance with all institutional animal care and use guidelines. After weaning, the mice were fed a chow diet until 8 weeks of age, at which time they were randomly assigned to one of three diet groups designated as PO, EO, or FO. Each diet contained 0.2% cholesterol and 10% of calories from PO with an additional 10% of calories from PO, EO, or

Echium oil feeding results in decreased plasma lipids and apoB lipoproteins

In our previous study, experimental diet feeding was limited to 8 weeks [6] and atherosclerosis was not evaluated. Here, we extended the feeding period to 16 weeks to investigate atherosclerosis development. Mice in all three diet groups gained body weight at similar rates (Fig. 1A). Plasma fatty acid compositions were similar to those reported previously [6], with mice fed EO exhibiting an enrichment in EPA, but not DHA, relative to those fed PO (Supplemental Fig. 1). Mice fed the EO diet had

Discussion

Due to the high incidence of cardiovascular disease and the low consumption of FO and/or fatty fish in the United States [2], the goal of our study was to determine whether EO could serve as a botanical source of n-3 PUFAs for atheroprotection. Using a mouse model of atherosclerosis, we show for the first time that EO feeding results in decreased atherosclerosis compared to mice fed PO and is equivalent in atheroprotection to FO.

Multiple health benefits of n-3 PUFAs have been demonstrated in

Acknowledgements

This work was funded by grant numbers P50 AT002782, R01 HL094525, and P01 HL049373 to JSP. Croda Chemicals provided the echium oil used in our diets and Omega Protein Inc. provided the OmegaPure refined menhaden oil for our FO diet. We gratefully acknowledge Karen Klein (Research Support Core, Wake Forest School of Medicine) for editing the manuscript.

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