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How does dietary carbohydrate influence the formation of an atherogenic lipoprotein phenotype?

膳食碳水化合物如何影响致动脉粥样硬化脂蛋白表型的形成？

基本信息

批准号：
BB/G009899/1
负责人：
Bruce Griffin
金额：
$ 83.35万
依托单位：
University of Surrey
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2009
资助国家：
英国
起止时间：
2009 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=BB%2FG009899%2F1
关键词：
How does dietary carbohydrate influence

项目摘要

Premature cardiovascular disease (CVD) is responsible for 1 in 3 deaths in the UK, and imposes an enormous financial burden on the NHS. Its prevalence is increasing at an alarming rate because of the CVD risk associated with obesity and related conditions such as diabetes. A key public health nutritional strategy for preventing the development of obesity and reducing CVD risk, is to replace dietary fat, principally saturated fat, with carbohydrate. However, studies have shown that when fat is replaced with carbohydrate, the risk of CVD actually increases. This effect has been linked to the quality of carbohydrate, and more specifically, to an increased intake of simple sugars such as sucrose and fructose. The latter are abundant in our diet and when overconsumed, have been shown to increase the amount of fat (triglyceride) in the blood and in tissues such as the liver. This accumulation of fat can lead to a metabolic defect that occurs in obesity and diabetes called insulin resistance, when tissues in the body become unresponsive to the actions of insulin. Insulin resistance is a very common condition that can produce adverse changes in cholesterol metabolism that increase the risk of developing CVD. These changes include an increase in particles known as small, dense LDL (sdLDL) that are found in high levels in the blood of people with obesity and diabetes, and transport cholesterol into the walls of blood vessels, causing CVD. Exactly how dietary carbohydrate increases the amount of fat in the blood and tissues such as liver, and contributes, with insulin resistance, to high levels of sdLDL is not clear. Answers to these questions would provide a better understanding of why the quality of carbohydrate is associated with increased CVD risk. They would also provide valuable information for influencing future dietary recommendations for public health. The aim of this research proposal is to determine the metabolic mechanisms by which the quality of dietary carbohydrate, high in simple sugars, increases blood fat and influences the formation of sdLDL. This will be studied in people with evidence of insulin resistance and an increased amount of liver fat. This study group is representative of a free-living and otherwise healthy UK population who are at increased risk of CVD. They are also known to be sensitive to the adverse effects of dietary carbohydrate, and thus stand to gain the greatest benefit from changing their diet in line with the results from this study. Our hypothesis states that a diet high in simple sugars will increase the number of sdLDL particles by increasing the amount of triglyceride-rich particles secreted from the liver (called VLDL1 particles), and that this will occur to a greater extent in people with insulin resistance and a moderate amount of liver fat. The study will compare two diets that are high and low in sugars but still representative of the UK diet. It will be a free-living study, with foods being supplied to the volunteers and consumed in their own homes. Subjects at increased risk of CVD will be subdivided into two groups with low and moderately raised liver fat, as measured by non-invasive MRI scanning. After a run-in diet low in simple sugars, subjects will be randomised to either continue on this run-in diet or switch to a diet high in simple sugars for 12 weeks. The subjects then switch to the other diet for another 12 weeks. Metabolic investigations to determine the mechanism by which the diet increases blood fat and forms sdLDL will be carried out at the end of each diet. This will involve giving the subjects stable istopes as trace labels to measure the rate at which triglyceride is produced in the liver, and to follow the metabolism of triglyceride-rich VLDL1 to determine exactly how this forms sdLDL under the two dietary conditions. These methods present no risk to the volunteers and will provide unique information to reduce the adverse effects of dietary carbohydrate on CVD

在英国，早发心血管疾病（CVD）造成三分之一的死亡，并给NHS带来了巨大的经济负担。由于与肥胖和糖尿病等相关疾病相关的心血管疾病风险，其患病率正以惊人的速度增加。预防肥胖和降低心血管疾病风险的一个关键公共卫生营养策略是用碳水化合物取代膳食脂肪，主要是饱和脂肪。然而，研究表明，当脂肪被碳水化合物取代时，CVD的风险实际上会增加。这种影响与碳水化合物的质量有关，更具体地说，与蔗糖和果糖等单糖的摄入量增加有关。后者在我们的饮食中很丰富，当过度食用时，已被证明会增加血液和肝脏等组织中的脂肪（甘油三酯）量。这种脂肪的积累会导致肥胖和糖尿病中发生的代谢缺陷，称为胰岛素抵抗，此时体内组织对胰岛素的作用没有反应。胰岛素抵抗是一种非常常见的疾病，可导致胆固醇代谢发生不良变化，从而增加发生CVD的风险。这些变化包括被称为小而密的低密度脂蛋白（sdLDL）的颗粒的增加，这些颗粒在肥胖和糖尿病患者的血液中含量很高，并将胆固醇转运到血管壁中，导致CVD。饮食中的碳水化合物究竟如何增加血液和肝脏等组织中的脂肪量，并与胰岛素抵抗一起导致高水平的sdLDL尚不清楚。这些问题的答案将有助于更好地理解为什么碳水化合物的质量与CVD风险增加有关。它们还将提供有价值的信息，影响未来的公共卫生饮食建议。这项研究的目的是确定膳食碳水化合物的质量，高糖，增加血脂和影响sdLDL形成的代谢机制。这将在有胰岛素抵抗证据和肝脏脂肪量增加的人中进行研究。该研究组代表了自由生活和其他健康的英国人群，他们的CVD风险增加。他们也被认为对饮食碳水化合物的不良影响敏感，因此根据这项研究的结果，他们可以从改变饮食中获得最大的好处。我们的假设表明，高糖饮食将通过增加肝脏分泌的富含脂蛋白的颗粒（称为VLDL 1颗粒）的数量来增加sdLDL颗粒的数量，并且这将在胰岛素抵抗和中等肝脏脂肪量的人群中更大程度地发生。这项研究将比较两种高糖和低糖的饮食，但仍然代表英国的饮食。这将是一项自由生活的研究，食物将提供给志愿者，并在他们自己的家中食用。CVD风险增加的受试者将被细分为两组，通过无创MRI扫描测量肝脏脂肪低和中度升高。在低单糖导入饮食后，受试者将被随机分配继续该导入饮食或转换为高糖饮食12周。然后，受试者转向另一种饮食，持续12周。将在每次饮食结束时进行代谢研究，以确定饮食增加血脂和形成sdLDL的机制。这将涉及给予受试者稳定的istopes作为痕量标记，以测量肝脏中甘油三酯产生的速率，并跟踪富含甘油三酯的VLDL 1的代谢，以准确确定在两种饮食条件下如何形成sdLDL。这些方法对志愿者没有风险，并将提供独特的信息，以减少饮食碳水化合物对心血管疾病的不良影响