FFA Production From Triglyceride-Rich Lipoproteins

从富含甘油三酯的脂蛋白生产 FFA

• 批准号: 6883985
• 负责人: JOHN M MILES
• 金额: $ 36.5万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-05-01 至 2007-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6883985
• 关键词: adipose tissue; blood lipoprotein metabolism; chylomicrons; clinical research; dietary lipid; exercise; fatty acid metabolism; fatty acid transport; free fatty acids; gastrointestinal nutrient absorption; human subject; insulin; lipoprotein lipase; muscle metabolism; noninsulin dependent diabetes mellitus; nutrition related tag; radiotracer; triglycerides; very low density lipoprotein

DESCRIPTION (provided by applicant): The proposed research will continue our work in the area of the regulation of fuel metabolism. Lipid energy is transported in the blood in several forms, including chylomicrons and free fatty acids (FFA). Chylomicrons are key elements in the absorption and storage of dietary fat, and also play a role in the pathogenesis of atherosclerosis via the production of remnant particles. FFA are the major lipid fuel in the body, and increases in their concentration have been shown to cause insulin resistance, endothelial dysfunction, increases in the production of very low density lipoproteins, and increases in blood pressure. FFA are released into the blood through the action of hormone sensitive lipase on triglyceride stores in fat cells. Very little is known about the role of chylomicrons in FFA metabolism, but available evidence suggests that chylomicrons are also a major source of FFA. Extremely accurate and precise methods have been developed by the investigator for the measurement of the concentration and specific activity of FFA and chylomicron triglyceride fatty acids in plasma. In addition, a tracer method for accurately determining the kinetics of chylomicrons has been developed. Preliminary results indicate that approximately 40% of chylomicron fatty acids are released into the circulation as FFA during their metabolism by lipoprotein lipase, and that this release may be greater in adipose tissue than in skeletal muscle. In the proposed studies, the tracer technique will be used to systematically investigate the contribution of chylomicrons to total FFA availability. The technique will be applied to normal subjects at rest and after exercise, as well as subjects with type 2 diabetes mellitus and hypertriglyceridemia. Specifically, these studies will 1) determine the relative contribution of chylomicrons in adipose tissue versus muscle to FFA production and further validate the isotopic method for quantifying chylomicron triglyceride kinetics; 2) determine the relationship between meal fat content and the production of FFA from chylomicrons; 3) characterize FFA production from chylomicrons in subjects with type 2 diabetes and the effect of acute insulin therapy on that process; and 4) determine whether exercise sufficient to lower the chylomicronemic response to a meal results in increased efficiency of regional and systemic chylomicron fatty acid uptake in normal subjects. These studies will provide new insights into the regulation of FFA metabolism in humans.

描述(由申请人提供)：拟议的研究将继续我们在燃料代谢调节领域的工作。脂肪能量在血液中以几种形式运输，包括乳糜粒和游离脂肪酸(FFA)。乳糜粒是膳食脂肪吸收和储存的关键元素，也通过产生残留颗粒在动脉粥样硬化的发病机制中发挥作用。游离脂肪酸是体内主要的脂肪燃料，其浓度的增加已被证明会导致胰岛素抵抗、内皮功能障碍、极低密度脂蛋白的产生增加和血压升高。游离脂肪酸通过激素敏感脂肪酶对储存在脂肪细胞中的甘油三酯的作用而释放到血液中。乳糜粒在FFA代谢中的作用知之甚少，但现有证据表明，乳糜粒也是FFA的主要来源。研究人员已经开发出极其准确和精密的方法来测量血浆中FFA和乳糜米隆甘油三酯脂肪酸的浓度和比活性。此外，还建立了一种准确测定乳胶粒动力学的示踪方法。初步结果表明，大约40%的乳胶体脂肪酸在其代谢过程中通过脂蛋白脂肪酶以FFA的形式释放到循环中，并且这种释放在脂肪组织中可能比在骨骼肌中更大。在拟议的研究中，将使用示踪剂技术来系统地调查乳胶粒对总FFA利用率的贡献。这项技术将应用于休息和运动后的正常受试者，以及2型糖尿病和高甘油三酯血症的受试者。具体地说，这些研究将1)确定脂肪组织相对于肌肉中乳糜微粒子对FFA产生的相对贡献，并进一步验证量化乳糜微粒子甘油三酯动力学的同位素方法；2)确定膳食脂肪含量与乳糜微粒子产生FFA之间的关系；3)表征2型糖尿病患者乳糜微粒子产生FFA的特征以及急性胰岛素治疗对这一过程的影响；4)确定足够的运动以降低乳糜微粒子对一餐的反应是否会导致正常人局部和全身乳糜粒脂肪酸摄取效率的提高。这些研究将为人类FFA代谢的调节提供新的见解。