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.

R01AG033761

2009-09-15

2014-08-31