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.

Agency
National Institute of Health (NIH)
Institute
National Center for Complementary & Alternative Medicine (NCCAM)
Type
Specialized Center (P50)
Project #
5P50AT002782-03
Application #
7405970
Study Section
Special Emphasis Panel (ZAT1)
Project Start
Project End
Budget Start
2007-04-01
Budget End
2008-03-31
Support Year
3
Fiscal Year
2007
Total Cost
$309,012
Indirect Cost
Name
Wake Forest University Health Sciences
Department
Type
DUNS #
937727907
City
Winston-Salem
State
NC
Country
United States
Zip Code
27157
Liu, Tao; Barrett, Nora A; Kanaoka, Yoshihide et al. (2018) Type 2 Cysteinyl Leukotriene Receptors Drive IL-33-Dependent Type 2 Immunopathology and Aspirin Sensitivity. J Immunol 200:915-927
Rahbar, Elaheh; Waits, Charlotte Mae K; Kirby Jr, Edward H et al. (2018) Allele-specific methylation in the FADS genomic region in DNA from human saliva, CD4+ cells, and total leukocytes. Clin Epigenetics 10:46
Shewale, Swapnil V; Brown, Amanda L; Bi, Xin et al. (2017) In vivo activation of leukocyte GPR120/FFAR4 by PUFAs has minimal impact on atherosclerosis in LDL receptor knockout mice. J Lipid Res 58:236-246
Chilton, Floyd H; Dutta, Rahul; Reynolds, Lindsay M et al. (2017) Precision Nutrition and Omega-3 Polyunsaturated Fatty Acids: A Case for Personalized Supplementation Approaches for the Prevention and Management of Human Diseases. Nutrients 9:
Samuchiwal, Sachin K; Balestrieri, Barbara; Raff, Hannah et al. (2017) Endogenous prostaglandin E2 amplifies IL-33 production by macrophages through an E prostanoid (EP)2/EP4-cAMP-EPAC-dependent pathway. J Biol Chem 292:8195-8206
Rahbar, Elaheh; Ainsworth, Hannah C; Howard, Timothy D et al. (2017) Uncovering the DNA methylation landscape in key regulatory regions within the FADS cluster. PLoS One 12:e0180903
Cui, Tao; Hester, Austin G; Seeds, Michael C et al. (2016) Impact of Genetic and Epigenetic Variations Within the FADS Cluster on the Composition and Metabolism of Polyunsaturated Fatty Acids in Prostate Cancer. Prostate 76:1182-91
Sergeant, Susan; Rahbar, Elaheh; Chilton, Floyd H (2016) Gamma-linolenic acid, Dihommo-gamma linolenic, Eicosanoids and Inflammatory Processes. Eur J Pharmacol 785:77-86
Miller, Leslie R; Jorgensen, Matthew J; Kaplan, Jay R et al. (2016) Alterations in levels and ratios of n-3 and n-6 polyunsaturated fatty acids in the temporal cortex and liver of vervet monkeys from birth to early adulthood. Physiol Behav 156:71-8
Sergeant, Susan; Ruczinski, Ingo; Ivester, Priscilla et al. (2016) Impact of methods used to express levels of circulating fatty acids on the degree and direction of associations with blood lipids in humans. Br J Nutr 115:251-61

Showing the most recent 10 out of 55 publications