Effects of amino acids on regional lipid metabolism

氨基酸对局部脂质代谢的影响

• 批准号: 8318129
• 负责人: Elisabet Borsheim
• 金额: $ 28.88万
• 依托单位: UNIVERSITY OF TEXAS MED BR GALVESTON
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-15 至 2013-07-26
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8318129
• 关键词: Acute; Address; Adipose tissue; Adult; Affect; Aging; American; Americas; Amino Acids; Blood; Blood capillaries; Body Weight; Body Weight decreased; Carbohydrates; Cause of Death; Childhood; Cholesterol; Chronic; Clinical; Complication; Coronary heart disease; Data; Diet; Education; Elderly; Endothelium; Essential Amino Acids; Exercise; Fat-Restricted Diet; Fatty acid glycerol esters; Foundations; Future; Goals; Health; Hepatic; Hypertriglyceridemia; Intake; Intervention; Investigation; Kinetics; Lipids; Lipolysis; Liver; Measures; Metabolic; Methodology; Methods; Muscle; NMR Spectroscopy; Nonesterified Fatty Acids; Nutrient; Obesity; Overweight; Persons; Placebos; Plasma; Population; Proteins; Relative (related person); Risk Factors; Sex Characteristics; Supplementation; Techniques; Testing; Time; Tissues; Tracer; Triglycerides; Very low density lipoprotein; Weight; Woman; Work; apolipoprotein B-100; base; capillary; improved; in vivo; lipid metabolism; lipoprotein lipase; men; novel; novel therapeutic intervention; oxidation; particle; programs; research study; response; stable isotope; uptake; very low density lipoprotein triglyceride; young adult

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.

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（血液中甘油三酸酯升高[TG]浓度升高）的机制，并针对这种情况找到新的治疗方法。冠心病（CHD）是美国男女最大的杀手。高甘油三酯血症是CHD的重要独立危险因素，女性甚至比男性更强大。与超重和肥胖一样，血浆TG水平的升高在衰老中很常见。在吸收后条件下，大多数血浆TG作为从肝脏分泌的非常低密度脂蛋白（VLDL）颗粒的组成部分，并逐渐被脂蛋白脂肪酶逐渐水解为肌肉和脂肪组织毛细血管毛细血管内皮中心。此后，自由脂肪酸被组织吸收并细胞内代谢。因此，血液中的TG浓度取决于VLDL的合成和分解。低碳水化合物饮食已显示出积极影响血浆脂质浓度，导致TG降低。但是，很难将碳水化合物与蛋白质摄入量升高的独立影响与体重变化中的含量升高。我们发现，补充正常体重维持饮食的饮食量相对较少，氨基酸改善了老年人的脂质谱。具体而言，血浆TG浓度和肝脂质含量相对于起始水平降低。基本机制尚不清楚。我们开发了可靠地测量VLDL-TG和VLDL-APOB-100合成和分解的方法。这项研究的总体目的是确定氨基酸是否通过加速VLDL转换来改善脂质代谢谱。这项研究将确定氨基酸摄入量对VLDL-TG和VLDL-APOB-100的周转率以及对氨基酸反应的潜在性别差异的急性和慢性作用。高甘油三酸酯血症的老年受试者将与氨基酸或安慰剂补充进行为期8周的干预。主要方法论方法包括稳定的同位素示踪技术，以量化体内区域脂质代谢的动力学反应和核磁共振光谱，以量化肝脏TG。这项研究有可能构成高甘油三酯血症的新治疗方法的基础。公共卫生相关性：血液中的脂肪水平升高是冠心病的危险因素，冠心病是美国的主要死亡原因。该项目的总体目标是使用营养素（氨基酸）对男性和女性中这种情况进行补充的新型治疗，并了解这种治疗方法的工作原理。