Effects of amino acids on regional lipid metabolism

描述（由申请人提供）：该项目的总体目标是了解高甘油三酯血症（血液中甘油三酯[TG]浓度升高）的机制，并找到针对这种情况的新治疗方法。冠心病（CHD）是美国男性和女性最大的单一杀手。高甘油三酯血症是冠心病的重要独立危险因素，女性比男性更明显。随着年龄的增长，血浆TG水平的升高是很常见的，超重和肥胖也是如此。在吸收后的条件下，大多数血浆TG作为肝脏分泌的极低密度脂蛋白（VLDL）颗粒的组成部分循环，并逐渐被脂蛋白脂肪酶水解进入肌肉和脂肪组织毛细血管内皮。此后，游离脂肪酸被组织吸收并在细胞内代谢。因此，血液中的TG浓度依赖于VLDL的合成和分解。低碳水化合物饮食已被证明对血浆脂质浓度有积极影响，导致TG降低。然而，很难将缺乏碳水化合物与饮食中蛋白质摄入量增加以及体重变化的独立影响分开。我们发现，在维持正常体重的饮食中补充相对少量的氨基酸可以改善老年人的脂质状况。具体而言，血浆TG浓度和肝脏脂质含量相对于起始水平下降。潜在的机制尚不清楚。我们已经开发了可靠的方法来测量VLDL-TG和VLDL-ApoB-100的合成和分解同时和独立。本研究的总体目的是确定氨基酸是否通过加速VLDL的转换来改善脂质代谢谱。本研究将确定氨基酸摄入对VLDL-TG和VLDL-ApoB-100周转率的急性和慢性影响，以及对氨基酸反应的潜在性别差异。患有高甘油三酯血症的老年受试者将参加为期8周的氨基酸或安慰剂补充干预。主要的方法包括稳定同位素示踪技术来量化体内区域脂质代谢的动力学反应和核磁共振波谱来量化肝脏TG。这项研究有可能为高甘油三酯血症的新治疗方法奠定基础。公共卫生相关性：血液中脂肪水平升高是冠心病的危险因素，冠心病是美国人死亡的主要原因。这个项目的总体目标是测试一种新的治疗方法，即在男性和女性中使用营养（氨基酸）补充剂来治疗这种疾病，并了解这种治疗方法是如何起作用的。

DESCRIPTION (provided by applicant): The overall goal of this project is to understand mechanisms underlying hypertriglyceridemia (elevated triglyceride [TG] concentration in blood) and to find novel treatments against this condition. Coronary Heart Disease (CHD) is the single largest killer of American men and women. Hypertriglyceridemia is a significant independent risk factor for CHD, even stronger in women than in men. An increase in plasma TG level is common with aging, as with overweight and obesity. During postabsorptive conditions, most plasma TG circulates as a component of very low density lipoprotein (VLDL) particles secreted from the liver, and is gradually hydrolyzed by lipoprotein lipase into muscle and adipose tissue capillary endothelia. Thereafter, the free fatty acids are taken up by the tissue and metabolized intracellularly. TG concentration in blood is thus dependent on both the synthesis and breakdown of VLDL. Low carbohydrate diets have been shown to positively affect plasma lipid concentrations, resulting in decreased TG. However, it is difficult to separate the independent effects of absence of carbohydrates vs. elevated protein intake in the diet vs. changes in body weight. We have found that supplementing a normal weight maintaining diet with relatively small amounts of amino acids improved lipid profile in elderly. Specifically, plasma TG concentration and liver lipid content decreased relative to starting levels. The underlying mechanisms are not known. We have developed methods to reliably measure VLDL-TG and VLDL-ApoB-100 synthesis and breakdown simultaneously and independently. The general aim of this study is to determine if amino acids improve lipid metabolic profile by accelerating VLDL turnover. This study will determine acute and chronic effects of amino acid intake on turnover rates of VLDL-TG and VLDL-ApoB-100 and potential sex differences in the response to amino acids. Elderly subjects with hypertriglyceridemia will participate in an 8-week intervention with amino acids or placebo supplementation. Principal methodological approaches include stable isotope tracer techniques to quantify kinetic responses of regional lipid metabolism in vivo and nuclear magnetic resonance spectroscopy to quantify liver TG. This study has potential to form the basis of new therapeutic approaches to hypertriglyceridemia. PUBLIC HEALTH RELEVANCE: Elevated fat level in blood is a risk factor for coronary heart disease, a major cause of death in America. The overall goal of this project is to test a novel treatment using nutrient (amino acid) supplementation against this condition in men and women, and to understand how this treatment works.