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: 10683736
• 负责人: MICHAEL MILLER
• 金额: --
• 依托单位: PHILADELPHIA 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 2026-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10683736
• 关键词: Acceleration; 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; Coconut Oil; Collaborations; Confusion; 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; Inflammatory; Lipids; Lipoproteins; Macrophage; Mediating; Mediator; 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; cardiovascular disorder risk; cytokine; dietary; endothelial stem cell; experience; gut microbiome; heart disease risk; improved; indexing; insight; monocyte; monolayer; monounsaturated fat; oxidation; polyunsaturated fat; response; saturated fat; systemic inflammatory response; 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.

高脂血症（HTG）是退伍军人中的常见问题，与更大的 心血管疾病（CVD）的可能性。我们最近完成的VA Merit研究确定了一种饮食 富含非欧米茄3多不饱和脂肪（PUFA），上级单不饱和脂肪： 体重减轻，甘油三酯（TG）和血压降低;以及改善 代谢综合征退伍军人的内皮功能然而，不同的影响， 在HTG中还没有研究过脂肪组成不同的等热量膳食。因为餐后 脂血症（PPL）代表高度致动脉粥样硬化状态，HTG增加PPL的幅度; 区分富含饱和脂肪（SFA）、单不饱和脂肪（MUFA）和 多不饱和脂肪酸（PUFA）对动脉粥样硬化介质的作用与退伍军人高度相关， 增加CVD的风险。 具体目标如下： 具体目标1：检验富含SFA（椰子油）的脂肪餐将 与富含MUFA（高油酸向日葵油）或PUFA的脂肪餐相比， （鲑鱼油）。具体来说，我们假设富含MUFA或PUFA的膳食将产生 较小的PPL反应，下调全身性炎症的生物标志物的表达和水平， 炎症和血栓形成相比，SFA丰富的膳食与HTG退伍军人。的影响 在4周富含饱和脂肪的饮食阶段后，可能会加重。 具体目标2：检验富含SFA（椰子油）的脂肪餐会损害 与MUFA（高油酸向日葵油）或PUFA（鲑鱼油）相比，内皮功能。具体地说， 我们假设富含MUFA或PUFA的膳食将改善血流介导的血管舒张（FMD）， 和循环内皮祖细胞（EPCs）相比， 有HTG的退伍军人 具体目标3：研究调节对富含脂肪的 餐它们包括HDL功能（胆固醇流出、HDL氧化指数和对氧磷酶活性）， 脂解和转运蛋白活性（LPL、HL、CETP），单核细胞与内皮细胞的粘附 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 微生物组我们假设富含SFA椰子油的脂肪餐会损害这些功能， 参数在更大程度上比MUFA或PUFA丰富的膳食，这种影响可能是 在4周富含饱和脂肪的饮食阶段后加重。 该VA Merit提案利用了脂蛋白领域经验丰富的研究者之间的合作 代谢和营养生物化学。总的来说，这些研究有望推动我们的 了解富含脂肪的膳食对脂蛋白代谢的不同影响， 炎症、炎症的细胞和血管介质的分子表达、HDL和 血管内皮功能和致动脉粥样硬化的肠道代谢物在退伍军人中的作用。研究 对于那些被媒体搞糊涂的HTG退伍军人来说， 尽管缺乏数据支持其广泛的椰子油产品， 使用.