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

高甘油三酯血症(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)，在以下方面优于单一不饱和脂肪： 体重减轻，甘油三酯(TG)和血压下降；以及 患有代谢综合征的退伍军人的内皮功能。然而，一种 在HTG中，脂肪成分不同的等卡路里膳食尚未被研究。因为餐后 脂血症(PPL)代表高度的动脉粥样硬化状态，HTG增加PPL的幅度； 区分富含饱和脂肪(SFA)、单不饱和脂肪(MUFA)和 动脉粥样硬化介质上的多不饱和脂肪(PUFA)与退伍军人高度相关 心血管疾病风险增加。 具体目标如下： 具体目标1：检验富含SFA(椰子油)的脂肪餐是否会 与富含MUFA(高油酸葵花籽油)或PUFA的脂肪餐相比，强调PPL (三文鱼油)。具体地说，我们假设MUFA或PUFA强化膳食将产生 更小的PPL反应和下调系统性红斑狼疮生物标志物的表达和水平 HTG退伍军人的炎症和血栓形成与富含SFA的膳食的比较。其影响 在四周的富含饱和脂肪的饮食阶段后，这种情况可能会加重。 具体目标2：检验富含SFA(椰子油)的脂肪餐会损害人体健康的假设 内皮功能与MUFA(高油酸葵花籽油)或PUFA(三文鱼油)进行比较。具体来说， 我们假设MUFA或PUFA强化膳食将改善血流介导的血管扩张(FMD，)。 和循环内皮祖细胞(EPC)与富含SFA的膳食的比较 HTG的退伍军人。 具体目标3：研究基于脂质的调节对富含脂肪的反应的机制 吃饭。包括高密度脂蛋白功能(胆固醇外流、高密度脂蛋白氧化指数和对氧磷酶活性)， 脂蛋白溶解和转运蛋白活性(LPL、HL、CETP)、单核细胞与内皮细胞的黏附 内皮细胞和单核/巨噬细胞的单层、miRNA谱及其对肠道的影响 微生物组。我们假设，一顿富含SFA椰子油的肥肉会损害这些 这些参数在更大程度上超过了MUFA或PUFA强化膳食，而且这种影响可能是 在四周的饮食阶段富含饱和脂肪后加重。 退伍军人事务部的这项建议充分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，这些研究可望推动我们的 了解富含脂肪的膳食对脂蛋白代谢的不同影响 炎症，炎症细胞和血管介质的分子表达，高密度脂蛋白和 心血管疾病风险增加的退伍军人的内皮功能和致动脉粥样硬化的肠道代谢物。这项研究 对于被媒体迷惑的HTG退伍军人也可能有重要的实际意义 尽管缺乏数据支持椰子油产品的广泛传播，但仍有直销店倡导椰子油产品 使用。

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.