Effect of Differential Fat Loads on CVD Biomarkers in Veterans with HTG

差异脂肪负荷对接受 HTG 的退伍军人 CVD 生物标志物的影响

• 批准号: 9889253
• 负责人: MICHAEL MILLER
• 金额: --
• 依托单位: BALTIMORE VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9889253
• 关键词: Adhesions; Advocate; Age; American Heart Association; Arteries; Atherosclerosis; Biological Markers; Biological Process; Blood Pressure; Blood Vessels; Body Weight decreased; CETP gene; Cardiovascular Diseases; Cell Adhesion Molecules; Cholesterol; Chronic; Clinical Data; Coconut Oil; Collaborations; Data; Diet; Dietary Fats; Disease; Endothelial Cells; Endothelium; Exposure to; Fasting; Fatty acid glycerol esters; Gender; Heart Diseases; High Density Lipoproteins; Hour; Hypertriglyceridemia; Impairment; In Vitro; Inflammation; Inflammation Mediators; Lipids; Lipoproteins; Mediating; Mediator of activation protein; Metabolic; Metabolic syndrome; Metabolism; MicroRNAs; Molecular; Nutritional Biochemistry; Oils; Pathway interactions; Phase; Physiological; Process; Production; Proteins; Randomized; Research; Research Personnel; Risk; Role; Salmon; Serum; Signal Pathway; Sunflower Oil; Testing; Thrombosis; Time; Triglycerides; Up-Regulation; Vasodilation; Veterans; aryldialkylphosphatase; base; cardiovascular disorder risk; cytokine; endothelial stem cell; experience; gut microbiome; heart disease risk; improved; indexing; insight; macrophage; monocyte; monolayer; monounsaturated fat; oxidation; polyunsaturated fat; response; saturated fat; trimethyloxamine; uptake; vascular inflammation

Hypertriglyceridemia (HTG) is a common problem among Veterans and is associated with a greater likelihood of cardiovascular disease (CVD). Our recently completed VA Merit study identified a diet enriched in non-omega 3 polyunsaturated fat (PUFA) to be superior to monounsaturated fat for: weight loss, reductions in triglycerides (TG), and blood pressure; as well as improvement in endothelial function in Veterans with the metabolic syndrome. However, the differential effects of an isocaloric meal that varies in fat composition has not been studied in HTG. Because postprandial lipemia (PPL) represents a highly atherogenic state and HTG increases the magnitude of PPL; differentiating between fat meals enriched in saturated fat (SFA), monounsaturated fat (MUFA) and polyunsaturated fat (PUFA) on mediators of atherosclerosis is highly relevant to Veterans at increased risk of CVD. The Specific Aims are as follows: Specific Aim 1: To test the hypothesis that a fat meal enriched with SFA (coconut oil) will accentuate PPL compared to a fat meal enriched with MUFA (high oleic sunflower oil) or PUFA (salmon oil). Specifically, we hypothesize that a MUFA or PUFA enriched meal will produce a smaller PPL response and downregulate expression and levels of biomarkers of systemic inflammation and thrombosis compared to an SFA-enriched meal in Veterans with HTG. The effects are likely to be accentuated after a 4-week dietary phase enriched in saturated fat. Specific Aim 2: To test the hypothesis that a fat meal enriched with SFA (coconut oil) will impair endothelial function compared to MUFA (high oleic sunflower oil) or PUFA (salmon oil). Specifically, we hypothesize that a MUFA or PUFA enriched meal will improve flow-mediated vasodilation (FMD,) and circulating endothelial progenitor cells (EPCs) compared to a meal enriched with SFA in Veterans with HTG. Specific Aim 3: To study the lipid-based mechanisms modulating the response to a fat-enriched meal. They include HDL function (cholesterol efflux, HDL oxidation index and paraoxonase activity), lipolytic and transfer protein activity (LPL, HL, CETP), adhesion of monocytes to the endothelial monolayer, miRNA profiles in endothelial cells and monocyte/macrophages, and effects on the gut microbiome. We hypothesize that a fat meal enriched with SFA coconut oil will impair these parameters to a greater extent than MUFA or PUFA enriched meals, and that this effect is likely to be accentuated after a 4-week dietary phase enriched in saturated fat. This VA Merit proposal capitalizes on collaboration among experienced investigators in lipoprotein metabolism and nutritional biochemistry. Collectively, these studies are expected to advance our understanding of the differential effects of a fat-enriched meal on: lipoprotein metabolism, inflammation, molecular expression of cellular and vascular mediators of inflammation, HDL and endothelial function and atherogenic gut metabolites in Veterans at accelerated CVD risk. The study may also have important practical implications for Veterans with HTG who are confused by media outlets who advocate for coconut oil-based products despite the lack of data supporting its widespread use.

高甘油三酯血症（HTG）在退伍军人中是一个常见的问题，并与更大的