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）是退伍军人中常见的问题，与更大的相关 心血管疾病（CVD）的可能性。我们最近完成的VA功绩研究确定了饮食 富含非欧洲3多不饱和脂肪（PUFA）的富含单不饱和脂肪的含量： 体重减轻，甘油三酸酯（TG）的减少和血压；以及改进 具有代谢综合征的退伍军人的内皮功能。但是， 在HTG中尚未研究在脂肪成分中变化的等离子餐。因为餐后 脂肪血症（PPL）代表高度动脉粥样硬化状态，HTG增加了PPL的幅度。 区分富含饱和脂肪的脂肪粉（SFA），单不饱和脂肪（MUFA）和 动脉粥样硬化介体的多不饱和脂肪（PUFA）与退伍军人高度相关 CVD的风险增加。 具体目的如下： 特定目的1：测试以下假设：富含SFA（椰子油）的脂肪粉 与富含MUFA（高油酸向日葵油）或PUFA的脂肪粉相比，PPL的强调 （鲑鱼油）。具体而言，我们假设MUFA或PUFA富含餐会产生 较小的ppl响应和全身性生物标志物的表达和水平下调 与HTG的退伍军人中富含SFA的餐食相比，炎症和血栓形成。效果 在富含饱和脂肪的4周饮食阶段后，可能会突出。 特定目的2：检验以下假设：富含SFA（椰子油）的脂肪粉会损害 与MUFA（高油酸向日葵油）或PUFA（鲑鱼油）相比，内皮功能。具体来说， 我们假设MUFA或PUFA富含餐将改善流量介导的血管舒张（FMD，） 与富含SFA的餐食相比，循环内皮祖细胞（EPC） 与HTG的退伍军人。 特定目的3：研究基于脂质的机制调节对富含脂肪的反应的反应 一顿饭。它们包括HDL功能（胆固醇外排，HDL氧化指数和副氧源酶活性）， 脂溶剂和转移蛋白活性（LPL，HL，CETP），单核细胞粘附于内皮 单层，内皮细胞和单核细胞/巨噬细胞中的miRNA谱，以及对肠道的影响 微生物组。我们假设一顿富含SFA椰子油的脂肪会损害这些 参数比Mufa或Pufa富含餐的参数更大，并且这种效果可能是 在饱和脂肪中富含4周的饮食阶段后，突出了。 该VA优点提案资本利用了经验丰富的脂蛋白研究人员的合作 代谢和营养生物化学。总的来说，这些研究有望促进我们的 了解富含脂肪餐对脂蛋白代谢的差异作用， 炎症，炎症，HDL和血管介质的分子表达 CVD风险加速的退伍军人中的内皮功能和动脉粥样硬化代谢物。研究 对于与媒体混淆的HTG的退伍军人可能还具有重要的实际意义 尽管缺乏支持其广泛支持的数据，但倡导椰子油产品的媒体 使用。