EFFECT OF AMINO ACID INTAKE ON VLDL TURNOVER

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 中心，不一定是研究者的机构。 背景：极低密度脂蛋白（VLDL）由肝脏产生并分泌到血液中。VLDL颗粒含有蛋白质和甘油三酯（脂质）。它们通过血液循环，将甘油三酯转化为脂肪和肌肉组织。血液中甘油三酯水平升高是冠心病的危险因素。我们以前已经表明，饮食中补充氨基酸可以降低甘油三酯和VLDL的血浆浓度，但尚不清楚为什么会发生这种情况。 假设：一般假设是氨基酸摄入通过增加VLDL从肝脏转运的速率和/或甘油三酯摄取到其他组织（例如肌肉）的速率来降低血浆和肝脏甘油三酯。 具体目的和程序（总结）：本研究的目的是确定VLDL从肝脏转运出的速率和VLDL从血液中的清除率，并研究氨基酸摄入如何影响这些速率。10名55岁或以上的志愿者将分别参加一项研究。将注入脂肪酸和氨基酸的稳定同位素，并从血液和呼吸中进行测量。 实验设计（总结）：将通过UTMB OAIC招募核心招募最多20名55岁或以上的受试者，并入组研究。 为了确定输注研究的合格性，他们将首先在一般临床研究中心（GCRC）进行体格检查，包括血液样本和尿液样本。还将通过口服葡萄糖耐量试验测量胰岛素敏感性，并通过双能X射线吸收测定法（DEXA）测量身体组成。此后，10名受试者将完成11小时输注研究。志愿者将在研究当天上午进入GCRC。输注研究包括放置两根导管，每只手臂一根，采集血液样本，输注与白蛋白结合的氨基酸和脂肪酸的稳定同位素（天然存在的化合物，无放射性），测量呼吸中的氧气和二氧化碳，以及摄入氨基酸。实验期间将抽取约250 ml血液（约+献血量）。通过在高度复杂的仪器中研究血液样本以测量血液中稳定同位素的少量水平，PI和Co-Is将能够计算VLDL从肝脏中运输出来的速率和VLDL从血液中的清除率。 意义（总结）：了解蛋白质/氨基酸摄入如何影响脂质代谢具有重要意义。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.