EFFECT OF AMINO ACID INTAKE ON VLDL TURNOVER

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 背景：极低密度脂蛋白(VLDL)由肝脏产生并分泌到血液中。极低密度脂蛋白颗粒同时含有蛋白质和甘油三酯(脂)。它们在血液中循环，将甘油三酯释放给脂肪和肌肉组织。血液中甘油三酯水平的升高是冠心病的一个危险因素。我们之前已经证明，饮食中补充氨基酸可以降低血浆中甘油三酯和极低密度脂蛋白的浓度，但还不知道为什么会发生这种情况。 假设：一般的假设是，氨基酸摄入通过增加极低密度脂蛋白从肝脏转运出去的速率和/或甘油三酯吸收到其他组织(如肌肉)的速率来降低血浆和肝脏甘油三酯。 具体目标和程序(摘要)：这项研究的目的是确定极低密度脂蛋白从肝脏转运出去的速度和极低密度脂蛋白从血液中的清除速度，并调查氨基酸的摄入如何影响这些速度。十名55岁或以上的志愿者将每人参与一项研究。将注入稳定的脂肪酸和氨基酸同位素，并从血液和呼吸中进行测量。 实验设计(摘要)：将通过UTMB OAIC招募核心招募多达20名55岁或以上的受试者，并将其纳入研究。为了确定输液研究的资格，他们将首先在综合临床研究中心(GCRC)进行体检，包括血样和尿样。对胰岛素的敏感性也将通过口服葡萄糖耐量试验来测量，身体成分将通过双能X射线吸收法(DEXA)来测量。之后，10名受试者将完成11小时的输液研究。志愿者将在研究的上午来到GCRC。输液研究包括放置两根导管，每只手臂一根，采集血液样本，输入与白蛋白结合的氨基酸和脂肪酸的稳定同位素(天然化合物，没有放射性)，测量呼吸中的氧气和二氧化碳，以及摄取氨基酸。在实验期间将抽取大约250毫升的血液(大约是献血的+)。通过在高度精密的仪器中研究血液样本，以测量血液中少量稳定同位素的水平，PI和Co-IS将能够计算极低密度脂蛋白从肝脏转运出去的速度和极低密度脂蛋白从血液中的清除速度。 意义(摘要)：了解蛋白质/氨基酸摄入如何影响脂肪代谢具有重要意义。这可能对未来的饮食建议具有重要意义，以防止血浆中甘油三酯浓度升高，从而降低冠心病的风险。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Background: Very low density lipoproteins (VLDL) are produced by the liver and secreted into the blood. VLDL particles contain both protein and triglycerides (lipids). They circulate through the blood giving up their triglycerides to fat and muscle tissue. An elevated level of triglycerides in the blood is a risk factor for coronary heart diseases. We have previously shown that amino acid supplementation of the diet can lower the plasma concentrations of triglycerides and VLDL, but it is not known why this happen. Hypothesis: The general hypothesis is that amino acid intake lowers plasma and liver triglycerides by increasing the rate of VLDL transport out of the liver and/or the rate of triglyceride uptake into other tissues, e.g. muscles. Specific Aims and Procedures (summary): The purpose of this study is to determine the rates of VLDL transport out of the liver and the clearance of VLDL from the blood, and also investigate how ingestion of amino acids affects these rates. Ten volunteers 55 years or older will take part in one study each. Stable isotopes of fatty acids and amino acids will be infused, and measurements will be taken from the blood and breath. Experimental Design (summary): Up to twenty subjects 55 years or older will be recruited through the UTMB OAIC recruitment core and enrolled in the study. To determine eligibility for an infusion study, they will first have a physical examination at the General Clinical Research Center (GCRC), including a blood sample and a urine sample. The sensitivity for insulin will also be measured by an oral glucose tolerance test, and body composition will be measured by Dual Energy X-Ray Absorptiometry (DEXA). Ten subjects will thereafter complete an 11 hour infusion study. The volunteer will come in to GCRC in the morning of the study. The infusion study involves the placement of two catheters, one in each arm, the taking of blood samples, infusion of stable isotopes (which are naturally occurring compounds and are not radioactive) of amino acids and fatty acids bound to albumin, measurement of oxygen and carbon dioxide in the breath, and ingestion of amino acids. About 250 ml of blood (approximately + of a blood donation) will be drawn during the experiment. By studying the blood samples in highly sophisticated instruments to measure the small level of stable isotopes in the blood, the PI and Co-Is will be able to calculate the rates of VLDL transport out of the liver and the clearance of VLDL from the blood. Significance (summary): It is of significance to understand how protein/amino acid intake affects lipid metabolism. This may be of importance for future diet recommendations to prevent elevated triglyceride concentrations in plasma, and thus also reduce the risk for coronary heart diseases.