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Grant Abstract

Grant Number: 5P50AT002782-03
Project Title: Project 2- Echium Oil Triglyceride Metabolism

Abstract: Consumption of n-3 polyunsaturated fatty acid (PUFA) supplements enriched in 20:5 n-3 (EPA) and 22:6 n-3 (DMA) has been shown to reduce coronary heart disease (CHD) and plasma triglyceride (TG) concentrations. Despite the beneficial effects of n-3 PUFAs, consumption in the American population remains low. Vegetable oils containing 18:3 n-3 (alpha-LNA) have only limited impact on tissue concentrations of EPA and DHA, since the conversion of alpha-LNA to EPA is limited by the inefficiency of the delta-6 desaturase-catalyzed step. One strategy to enrich tissues in EPA and DHA is to use botanical oils that are enriched in fatty acids that bypass the delta-6 desaturase step of fatty acid elongation and desaturation. Echium oil, derived from the seeds of Echium Plantagineum, is enriched in stearidonic acid (SDA; 18:4 n-3), which is the immediate product of delta-6 desaturation of alpha-LNA. Our preliminary studies in hypertriglyceridemic human subjects have demonstrated that echium oil supplementation resulted in lower plasma TG concentrations. The goals of this project are to determine the mechanisms by which echium oil reduces plasma TG concentrations and whether echium oil supplementation will retard atherosclerosis progression relative to palm oil and fish oil (controls). The moderately hypertriglyceridemic apoB100 only-LDL receptor knockout (B100-LDLrKO) mouse will be used of these studies. In specific aim 1, we will test the hypothesis that echium oil supplementation will reduce plasma TG concentrations to a degree similar to that observed with fish oil supplementation. In specific aim 2, we will test the hypothesis that echium oil supplementation decreases plasma TG concentrations by down regulation of genes involved in hepatic TG synthesis, resulting in less hepatic TG synthesis and reduced VLDL TG secretion. In specific aim 3, we will test the hypothesis that echium oil supplementation will increase the lipolysis and catabolism of plasma TG enriched lipoproteins. In specific aim 4. we will test the hypothesis that echium oil supplementation will reduce aortic atherosclerosis. If echium oil supplementation proves to be atheroprotective, it could be used in conjunction with dietary guidelines to meet the AHA suggested intake of n-3 fatty acids necessary for cardioprotection.

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