Dietary Fat and HDL Metabolism

膳食脂肪和高密度脂蛋白代谢

基本信息

  • 批准号:
    8121581
  • 负责人:
  • 金额:
    $ 76.48万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2010
  • 资助国家:
    美国
  • 起止时间:
    2010-08-09 至 2015-07-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Dietary Fat and HDL Metabolism. A great unanswered question in nutrition and cardiovascular disease (CVD) is how to interpret the increase in HDL cholesterol concentration that occurs when dietary unsaturated fat is increased and carbohydrate or protein is reduced. This apparent advantage of unsaturated fat is one reason why some experts favor high unsaturated fat diets compared to those with carbohydrate or protein. Other experts are not so confident that that a therapeutic intervention that raises HDL concentration invariably protects against atherosclerosis. There is a sense of discomfort using simple changes in HDL cholesterol for nutrition and health policy. Lack of clarity of the underlying physiology interferes with informed opinion. There are several metabolic pathways that can sustain a high HDL concentration. It is unclear how dietary fat affects them. The critical issue is whether dietary fat improves the steps in HDL metabolism that are involved in reverse cholesterol transport that protects against atherosclerosis. HDL is indisputably a necessary component of the cholesterol transport and homeostatic system, and a low HDL concentration is one of the strongest predictors of high risk of CVD. Low HDL cholesterol is prominent in overweight and obesity, insulin resistance, type 2 diabetes, and metabolic syndrome. This low HDL concentration is associated with accelerated clearance from the blood circulation of HDL particles, measured by their principal protein, apolipoprotein A-I, and a preponderance of small HDL. This suggests a block in the maturation of HDL from small cholesterol-depleted to large cholesterol ester-rich particles, and impaired reverse cholesterol transport. We do not know whether dietary unsaturated fat corrects this dysfunctional metabolism of HDL. We propose a clinical intervention study in 20 people who have low HDL cholesterol concentrations in the typical setting of overweight or obesity, and high plasma triglycerides to determine how dietary unsaturated fat increases their HDL concentration. We will use stable isotopic tracers to label endogenously apolipoprotein A-I, the defining protein of HDL, to trace its metabolism from small nascent particles ("pre-beta HDL") to large, cholesterol-loaded mature particles ("alpha 1,2, and 3 HDL"), and evaluate the extent of the reverse process representing selective removal of cholesterol ester by the liver. We will study whether dietary fat reduces the involvement of apolipoprotein C-III in HDL metabolism. HDL that has apoC-III has an adverse association with CVD, opposite to the major HDL type that does not have apoC-III. This information will prove invaluable in interpreting the established HDL-raising effect of dietary fat in terms of protection against atherosclerosis. PUBLIC HEALTH RELEVANCE: Dietary fat and HDL metabolism The goal of this proposal is to determine the mechanisms by which unsaturated fat in the diet increases blood concentrations of high density lipoprotein (HDL), a protective lipoprotein that removes cholesterol from atherosclerosis, and reduces risk of cardiovascular disease. The project is a controlled diet study comparing a high unsaturated fat diet with a high carbohydrate diet. Direct metabolic studies of HDL in humans that trace its metabolism will be conducted at the end of each diet. The goal is to develop a detailed picture of how unsaturated fat raises HDL and protects against cardiovascular disease.
描述(由申请人提供):膳食脂肪和高密度脂蛋白代谢。在营养学和心血管疾病(CVD)中,一个悬而未决的问题是如何解释当饮食中不饱和脂肪增加而碳水化合物或蛋白质减少时高密度脂蛋白胆固醇浓度的增加。不饱和脂肪的这种明显优势是一些专家青睐高不饱和脂肪饮食而不是碳水化合物或蛋白质饮食的原因之一。另一些专家则对提高高密度脂蛋白浓度的治疗干预一定能预防动脉粥样硬化不那么有信心。通过对高密度脂蛋白胆固醇的简单改变来制定营养和健康政策,会让人感到不舒服。缺乏对潜在生理学的清晰了解会干扰有根据的意见。有几种代谢途径可以维持高HDL浓度。目前还不清楚膳食脂肪是如何影响它们的。关键的问题是膳食脂肪是否能改善高密度脂蛋白代谢的步骤,而高密度脂蛋白代谢与胆固醇的逆向运输有关,从而防止动脉粥样硬化。HDL无疑是胆固醇运输和体内平衡系统的必要组成部分,低HDL浓度是心血管疾病高风险的最强预测因子之一。低高密度脂蛋白胆固醇在超重和肥胖、胰岛素抵抗、2型糖尿病和代谢综合征中很突出。这种低HDL浓度与血液循环中HDL颗粒的加速清除有关,通过它们的主要蛋白,载脂蛋白a - i和小HDL的优势来测量。这表明HDL从小的胆固醇耗尽颗粒到大的富含胆固醇酯颗粒的成熟受到阻碍,并损害了胆固醇的逆向运输。我们不知道饮食中的不饱和脂肪是否能纠正高密度脂蛋白代谢的失调。我们提出了一项临床干预研究,对20名典型超重或肥胖的低HDL胆固醇浓度和高血浆甘油三酯的人进行研究,以确定饮食不饱和脂肪如何增加他们的HDL浓度。我们将使用稳定的同位素示踪剂来标记内源性载脂蛋白A-I(高密度脂蛋白的定义蛋白),以追踪其从小的新生颗粒(“前- β - HDL”)到大的,装载胆固醇的成熟颗粒(“α 1,2和3 HDL”)的代谢,并评估肝脏选择性去除胆固醇酯的反向过程的程度。我们将研究膳食脂肪是否会减少载脂蛋白C-III在HDL代谢中的参与。与不含apoC-III的主要HDL类型相反,含有apoC-III的HDL与CVD有不良关联。这一信息对于解释膳食脂肪在预防动脉粥样硬化方面提高高密度脂蛋白的作用是非常宝贵的。

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

FRANK M SACKS其他文献

FRANK M SACKS的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('FRANK M SACKS', 18)}}的其他基金

Intervention Core for the Dietary Biomarkers Development Center at Harvard University
哈佛大学膳食生物标志物开发中心的干预核心
  • 批准号:
    10289795
  • 财政年份:
    2021
  • 资助金额:
    $ 76.48万
  • 项目类别:
Intervention Core for the Dietary Biomarkers Development Center at Harvard University
哈佛大学膳食生物标志物开发中心的干预核心
  • 批准号:
    10461133
  • 财政年份:
    2021
  • 资助金额:
    $ 76.48万
  • 项目类别:
Intervention Core for the Dietary Biomarkers Development Center at Harvard University
哈佛大学膳食生物标志物开发中心的干预核心
  • 批准号:
    10649588
  • 财政年份:
    2021
  • 资助金额:
    $ 76.48万
  • 项目类别:
HDL Proteins and Coronary Heart Disease
HDL 蛋白与冠心病
  • 批准号:
    8916827
  • 财政年份:
    2014
  • 资助金额:
    $ 76.48万
  • 项目类别:
HDL Proteins and Coronary Heart Disease
HDL 蛋白与冠心病
  • 批准号:
    8753171
  • 财政年份:
    2014
  • 资助金额:
    $ 76.48万
  • 项目类别:
Dietary Fat and HDL Metabolism
膳食脂肪和高密度脂蛋白代谢
  • 批准号:
    8688317
  • 财政年份:
    2010
  • 资助金额:
    $ 76.48万
  • 项目类别:
Dietary Fat and HDL Metabolism
膳食脂肪和高密度脂蛋白代谢
  • 批准号:
    8314034
  • 财政年份:
    2010
  • 资助金额:
    $ 76.48万
  • 项目类别:
Dietary Fat and HDL Metabolism
膳食脂肪和高密度脂蛋白代谢
  • 批准号:
    8496098
  • 财政年份:
    2010
  • 资助金额:
    $ 76.48万
  • 项目类别:
Dietary Fat and HDL Metabolism
膳食脂肪和高密度脂蛋白代谢
  • 批准号:
    7987093
  • 财政年份:
    2010
  • 资助金额:
    $ 76.48万
  • 项目类别:
POUNDS LOST
减磅
  • 批准号:
    7719326
  • 财政年份:
    2008
  • 资助金额:
    $ 76.48万
  • 项目类别:

相似海外基金

Alpha particles combined with ATR inhibition to activate the immune system: mechanisms and pre-clinical translation
Alpha 粒子结合 ATR 抑制激活免疫系统:机制和临床前转化
  • 批准号:
    10636348
  • 财政年份:
    2023
  • 资助金额:
    $ 76.48万
  • 项目类别:
Long range detection of alpha particles.
阿尔法粒子的远距离检测。
  • 批准号:
    ST/W005050/1
  • 财政年份:
    2022
  • 资助金额:
    $ 76.48万
  • 项目类别:
    Training Grant
Elucidation of unusual nano-effects on dissolution, aggregation and denaturation processes of alpha particles generated by fuel debris retrieval
阐明燃料碎片回收产生的α粒子溶解、聚集和变性过程中异常纳米效应
  • 批准号:
    EP/X022218/1
  • 财政年份:
    2022
  • 资助金额:
    $ 76.48万
  • 项目类别:
    Research Grant
Integrated modelling of burning plasmas with a reduced transport model for alpha particles
燃烧等离子体的集成建模与α粒子的简化传输模型
  • 批准号:
    15K18311
  • 财政年份:
    2015
  • 资助金额:
    $ 76.48万
  • 项目类别:
    Grant-in-Aid for Young Scientists (B)
SHINE: Self-Consistent Resonant-Cyclotron Heating of Protons and Alpha Particles in the Solar Wind and Solar Corona
SHINE:太阳风和日冕中质子和阿尔法粒子的自洽共振回旋加热
  • 批准号:
    1358103
  • 财政年份:
    2014
  • 资助金额:
    $ 76.48万
  • 项目类别:
    Continuing Grant
Basic Study to evaluate DNA Damage and Cell Survival with Alpha-Particles from Astatine-211
使用 Astatine-211 的 α 粒子评估 DNA 损伤和细胞存活的基础研究
  • 批准号:
    26461866
  • 财政年份:
    2014
  • 资助金额:
    $ 76.48万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Study of the alpha cluster gas-like state in 12C via the measurement of the multiple decay alpha particles
通过多次衰变α粒子的测量研究12C中的α团簇气态
  • 批准号:
    24740139
  • 财政年份:
    2012
  • 资助金额:
    $ 76.48万
  • 项目类别:
    Grant-in-Aid for Young Scientists (B)
Theoretical study on dynamics of 12C synthesis through radiative capture reactions of three alpha-particles
三种α粒子辐射捕获反应合成12C动力学的理论研究
  • 批准号:
    24540261
  • 财政年份:
    2012
  • 资助金额:
    $ 76.48万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Analysis of ripple resonance diffusion of alpha particles in burning plasma
燃烧等离子体中α粒子的波纹共振扩散分析
  • 批准号:
    21560856
  • 财政年份:
    2009
  • 资助金额:
    $ 76.48万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
NSWP: Kinetic Turbulence-Driven Solar Wind Model Through the Resonant Cyclotron Interaction - Protons and Alpha Particles
NSWP:通过共振回旋加速器相互作用的动力学湍流驱动的太阳风模型 - 质子和阿尔法粒子
  • 批准号:
    0719738
  • 财政年份:
    2007
  • 资助金额:
    $ 76.48万
  • 项目类别:
    Continuing Grant
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了