FFA Production From Triglyceride-Rich Lipoproteins

从富含甘油三酯的脂蛋白生产 FFA

基本信息

  • 批准号:
    8575973
  • 负责人:
  • 金额:
    $ 39.94万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2003
  • 资助国家:
    美国
  • 起止时间:
    2003-05-01 至 2017-06-30
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): The proposed research will continue our work in the area of the regulation of lipid fuel metabolism. Lipid energy is transported in the blood in severa 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, but their role as a direct fuel source has not been extensively investigated. FFAs are the major lipid fuel in the body, and increases in their concentration have been shown to cause insulin resistance, endothelial dysfunction and increases in the production of very low density lipoproteins. FFAs 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 the potential contribution of chylomicrons to FFA is considerable, especially in people who consume high fat diets. Initial studies indicate that in addition to the role of chylomicrons in fat storage, a portion of chylomicron fatty acids are released as FFA in a process called "spillover". A study of spillover in the splanchnic bed found very high rates of splanchnic spillover in overweight and obese individuals with hypertriglyceridemia. Subsequent studies have shown that intravenous infusion of niacin, a drug known to suppress FFA release, produced a significant reduction in fractional spillover, whereas insulin infusion had no effect. Furthermore, in people with type 2 diabetes spillover correlated negatively with leg fat - that is, individuals with a large amount of leg fat ad lower spillover (an indication of more efficient fat storage), while those with small amounts of le fat had higher spillover, indicating less efficient storage. No information is available on spillovr in lower body fat tissue, nor on its relationship with spillover in the splanchnic bed (which includes visceral fat). 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. 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 lean and obese subjects, including people who have undergone gastric bypass surgery. Specifically, these studies will: 1) determine whether weight loss after gastric bypass reduces spillover from chylomicrons; 2) determine whether acute lowering of FFA with niacin infusion reduces spillover in overweight and obese people; 3) determine whether women with upper body obesity have greater systemic spillover than women with lower body obesity, and whether body fat distribution determines chylomicron triglyceride uptake and spillover in leg and splanchnic fat and 4) determine whether women with upper body obesity gain less weight during supervised overfeeding than women with lower body obesity.
描述(由申请人提供):拟议的研究将继续我们在脂类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)。乳胶粒是食物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,但它们作为直接燃料来源的作用尚未得到广泛研究。游离脂肪酸是人体内的主要脂质燃料,其浓度的增加已被证明会导致胰岛素抵抗、内皮功能障碍和极低密度脂蛋白的产生增加。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,游离脂肪酸被释放到血液中。乳胶粒在FFA代谢中的作用知之甚少,但乳糜粒对FFA的潜在贡献是相当大的,特别是在食用高脂肪饮食的人中。初步研究表明,除了乳胶粒在脂肪储存中的作用外,乳糜粒脂肪酸的一部分在一个被称为“溢出”的过程中以FFA的形式被释放。一项关于内脏床溢出的研究发现,在患有高甘油三酯血症的超重和肥胖者中,内脏溢出的比率非常高。随后的研究表明,静脉输注烟酸,一种已知的抑制FFA释放的药物,产生显著的减少分数溢出,而胰岛素输注没有效果。此外,在2型糖尿病患者中,溢出效应与腿部脂肪呈负相关--即腿部脂肪含量较多且溢出效应较低的个体(这表明脂肪储存更有效),而脂肪含量较少的个体溢出效应较高,表明储存效率较低。没有关于下半身脂肪组织溢出的信息,也没有关于它与内脏床(包括内脏脂肪)溢出的关系的信息。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。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。这项技术将应用于瘦和肥胖的受试者,包括接受过胃旁路手术的人。具体地说,这些研究将:1)确定胃旁路手术后体重减轻是否减少乳糜粒的溢出效应;2)确定在超重和肥胖者中应用烟酸急剧降低FFA是否减少溢出效应;3)确定上半身肥胖者是否比下半身肥胖者有更大的全身外溢效应,以及体脂分布是否决定了乳糜米隆甘油三酯在腿部和内脏脂肪中的摄取和溢出;4)确定上半身肥胖者在有监督下超量喂养时体重增加是否少于下半身肥胖者。

项目成果

期刊论文数量(0)
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JOHN M MILES其他文献

JOHN M MILES的其他文献

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{{ truncateString('JOHN M MILES', 18)}}的其他基金

RELEASE OF FATTY ACIDS FROM CHYLOMICRONS IN FOREARM AND ADIPOSE TISSUE
前臂和脂肪组织中乳糜微粒释放脂肪酸
  • 批准号:
    7206155
  • 财政年份:
    2005
  • 资助金额:
    $ 39.94万
  • 项目类别:
THE ROLE OF PLASMA TRIGLYCERIDES IN MYOCARDIAL FUEL METABOLISM
血浆甘油三酯在心肌燃料代谢中的作用
  • 批准号:
    7206200
  • 财政年份:
    2005
  • 资助金额:
    $ 39.94万
  • 项目类别:
EFFECT OF INSULIN SENSITIZERS ON LIPID METABOLISM IN OBESE, DYSLIPIDEMIC SUBJECT
胰岛素增敏剂对肥胖、血脂异常受试者脂质代谢的影响
  • 批准号:
    7206162
  • 财政年份:
    2005
  • 资助金额:
    $ 39.94万
  • 项目类别:
FFA Production From Triglyceride-Rich Lipoproteins
从富含甘油三酯的脂蛋白生产 FFA
  • 批准号:
    6883985
  • 财政年份:
    2003
  • 资助金额:
    $ 39.94万
  • 项目类别:
FFA Production From Triglyceride-Rich Lipoproteins
从富含甘油三酯的脂蛋白生产 FFA
  • 批准号:
    7055229
  • 财政年份:
    2003
  • 资助金额:
    $ 39.94万
  • 项目类别:
Single IV Dose of ETC-642 in Stable Atherosclerosis
单次静脉注射 ETC-642 治疗稳定型动脉粥样硬化
  • 批准号:
    7042349
  • 财政年份:
    2003
  • 资助金额:
    $ 39.94万
  • 项目类别:
FFA Production From Triglyceride-Rich Lipoproteins
从富含甘油三酯的脂蛋白生产 FFA
  • 批准号:
    7588878
  • 财政年份:
    2003
  • 资助金额:
    $ 39.94万
  • 项目类别:
FFA Production From Triglyceride-Rich Lipoproteins
从富含甘油三酯的脂蛋白生产 FFA
  • 批准号:
    6736917
  • 财政年份:
    2003
  • 资助金额:
    $ 39.94万
  • 项目类别:
FFA Production From Triglyceride-Rich Lipoproteins
从富含甘油三酯的脂蛋白生产 FFA
  • 批准号:
    8282703
  • 财政年份:
    2003
  • 资助金额:
    $ 39.94万
  • 项目类别:
FFA Production From Triglyceride-Rich Lipoproteins
从富含甘油三酯的脂蛋白生产 FFA
  • 批准号:
    8054964
  • 财政年份:
    2003
  • 资助金额:
    $ 39.94万
  • 项目类别:

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