Effects of amino acids on regional lipid metabolism

氨基酸对局部脂质代谢的影响

• 批准号: 7751176
• 负责人: Elisabet Borsheim
• 金额: $ 30.35万
• 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 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7751176
• 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; Hepatic; Hydrolysis; 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); Research; 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; public health relevance; research study; response; stable isotope; uptake; 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）：本项目的总体目标是了解高甘油三酯血症（血液中甘油三酯[TG]浓度升高）的潜在机制，并找到针对这种疾病的新治疗方法。冠心病（CHD）是美国男性和女性的最大杀手。高脂血症是冠心病的一个重要的独立危险因素，在女性中甚至比男性更强。血浆TG水平的增加与衰老、超重和肥胖一样常见。在吸收后条件下，大多数血浆TG作为肝脏分泌的极低密度脂蛋白（VLDL）颗粒的组分循环，并逐渐被脂蛋白脂肪酶水解进入肌肉和脂肪组织毛细血管内皮。此后，游离脂肪酸被组织吸收并在细胞内代谢。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被证明对血浆脂质浓度有积极影响，导致TG降低。然而，很难区分饮食中碳水化合物缺乏与蛋白质摄入量增加与体重变化的独立影响。我们已经发现，补充一个正常的体重维持饮食与相对少量的氨基酸改善血脂老年人。具体来说，血浆TG浓度和肝脏脂质含量相对于起始水平下降。其潜在机制尚不清楚。我们已经开发出同时独立可靠地测量VLDL-TG和VLDL-ApoB-100合成和分解的方法。本研究的总体目的是确定氨基酸是否通过加速VLDL周转来改善脂质代谢谱。本研究将确定氨基酸摄入对VLDL-TG和VLDL-ApoB-100转换率的急性和慢性影响以及对氨基酸反应的潜在性别差异。患有高甘油三酯血症的老年受试者将参加为期8周的氨基酸或安慰剂补充干预。主要的方法包括稳定同位素示踪技术，以量化体内局部脂质代谢的动力学反应和核磁共振光谱，以量化肝脏TG。这项研究有可能形成新的治疗方法的基础上，高胆固醇血症。公共卫生相关性：血液中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测试一种新的治疗方法，使用营养素（氨基酸）补充剂来治疗男性和女性的这种疾病，并了解这种治疗方法是如何工作的。