This project is designed to identify atheroprotective effects of flaxseed oil. A mouse model of atherosclerosis, the B100+/+LDLr-/- mouse, will be studied to take advantage of similarities to humans in lipoprotein composition. The proposal is to directly compare flaxseed oil in diets providing 2% of energy as alpha-linolenic acid to a comparable diet containing enough fish oil to provide EPA+DHA as 2% of energy. Both of these diets will be compared to a diet containing saturated fat. Additional studies are proposed to find minimal effective levels of flaxseed oil required to demonstrate atheroprotection. All diets will contain 10% of energy as fat with no appreciable amounts of cholesterol added to the diets. We will examine diet-related differences in plasma lipid and lipoprotein metabolism, and we will study the diet response of liver lipid accumulation and secretion during recirculating perfusion. We will quantify the quality and extent of aortic atherosclerosis after 20 weeks of diet exposure. Based on preliminary data, we hypothesize that flaxseed oil will provide protection against development of atherosclerosis in spite of minimal effects on plasma lipid concentrations but significant effects on liver lipid compositions. We anticipate that flaxseed oil and fish oil-related differences in plasma lipoprotein composition will be identified that may predict decreased atherosclerosis. Further, we will examine macrophage inflammatory responses to the flaxseed oil and fish oil diets and detail mechanisms through which the ALA from flaxseed oil and EPA+DHA from fish oil could limit atherosclerosis.

Agency
National Institute of Health (NIH)
Institute
National Center for Complementary & Alternative Medicine (NCCAM)
Type
Specialized Center (P50)
Project #
5P50AT002782-04
Application #
7626051
Study Section
Special Emphasis Panel (ZAT1)
Project Start
Project End
Budget Start
2008-04-01
Budget End
2009-03-31
Support Year
4
Fiscal Year
2008
Total Cost
$271,371
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
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
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
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