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: 10578876
• 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 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10578876
• 关键词: Effect; Differential; Fat; Loads; CVD

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）是退伍军人中的一个常见问题，并且与更大的 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 omega 3 多不饱和脂肪 (PUFA)，在以下方面优于单不饱和脂肪： 体重减轻、甘油三酯 (TG) 降低和血压降低；以及改进 患有代谢综合征的退伍军人的内皮功能。然而，不同的影响 尚未在 HTG 中研究脂肪成分不同的等热量膳食。因为餐后 脂血症 (PPL) 代表高度动脉粥样硬化状态，HTG 会增加 PPL 的程度； 区分富含饱和脂肪（SFA）、单不饱和脂肪（MUFA）和 动脉粥样硬化介质中的多不饱和脂肪 (PUFA) 与退伍军人高度相关 CVD 风险增加。 具体目标如下： 具体目标 1：检验富含 SFA（椰子油）的脂肪餐会降低脂肪含量的假设 与富含 MUFA（高油酸葵花籽油）或 PUFA 的脂肪餐相比，强调 PPL （鲑鱼油）。具体来说，我们假设富含 MUFA 或 PUFA 的膳食会产生 较小的 PPL 反应并下调系统性生物标志物的表达和水平 与患有 HTG 的退伍军人相比，富含 SFA 的膳食可减少炎症和血栓形成。效果 经过 4 周富含饱和脂肪的饮食阶段后，这种情况可能会加剧。 具体目标 2：检验富含 SFA（椰子油）的脂肪餐会损害健康的假设 与 MUFA（高油酸葵花籽油）或 PUFA（鲑鱼油）相比，内皮功能更佳。具体来说， 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) 与富含 SFA 的膳食相比，循环内皮祖细胞 (EPC) 患有 HTG 的退伍军人。 具体目标 3：研究调节对富含脂肪的反应的脂质机制 一顿饭。它们包括 HDL 功能（胆固醇流出、HDL 氧化指数和对氧磷酶活性）、 脂肪分解和转移蛋白活性（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 参数的程度比富含 MUFA 或 PUFA 的膳食更大，并且这种效果可能是 经过 4 周富含饱和脂肪的饮食阶段后，这种情况更加严重。 VA Merit 提案利用了脂蛋白领域经验丰富的研究人员之间的合作 代谢和营养生物化学。总的来说，这些研究预计将推进我们的研究 了解富含脂肪的膳食对以下方面的不同影响：脂蛋白代谢， 炎症、炎症细胞和血管介质的分子表达、HDL 和 心血管疾病风险加速的退伍军人的内皮功能和致动脉粥样硬化肠道代谢物。研究 可能对那些被媒体迷惑的患有 HTG 的退伍军人也有重要的实际意义 尽管缺乏数据支持其广泛传播，但仍提倡椰子油产品的媒体 使用。