This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor 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.
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