Fatty acid sources of fructose and HFCS-induced postprandial hypertriglyceridemia

描述（由申请人提供）：这项拟议的辅助研究的母研究是NIH/ nhlbi资助的一项研究，比较年轻（18-40岁），正常体重和超重/肥胖成年人饮用含糖饮料2周的影响（5R01HL091333-02: 2周果糖和高果糖玉米糖浆摄入对脂质失调和胰岛素抵抗的影响）。基线实验程序（包括24小时连续血液采样）在受试者作为ctsc资助的临床研究中心（CCRC）住院患者居住3.5天，并消耗能量平衡，高复杂碳水化合物饮食期间进行。然后，受试者饮用含糖饮料，以果糖、葡萄糖或高果糖玉米糖浆（HFCS）的形式提供25%的能量需求；或10%或17.5%的能量作为果糖或高果糖玉米糖浆，以及他们通常的随意饮食。在为期两周的干预结束时，受试者回到CCRC并进行相同的实验程序，同时受试者消耗能量均衡的饮食，其中包括指定的含糖饮料。该研究的早期结果表明，以25%的能量摄入含hfcs的饮料会导致深夜餐后甘油三酯（TG）浓度、空腹低密度脂蛋白胆固醇和载脂蛋白b （ApoB）浓度的显著增加，其幅度与饮用含100%果糖的饮料后观察到的结果相当。饮用含葡萄糖饮料不会改变这些参数。有大量证据支持餐后高甘油三酯血症是导致代谢综合征和2型糖尿病特征的脂质失调的关键代谢紊乱的假设。本研究旨在研究果糖和高果糖玉米糖浆摄入导致餐后高甘油三酯血症的机制，方法是量化脂肪从头脂肪生成（DNL）、饮食和脂肪TG脂解产生的游离脂肪酸（FFA）对空腹和餐后富甘油三酯脂蛋白（TRL）水平的绝对贡献和比例贡献。稳定同位素将在24小时连续血液采样方案中（通过口服和26小时静脉输注）给予受试者亚组，该方案在所有研究参与者基线时消耗能量平衡、高复杂碳水化合物餐，以及在干预结束时饮用含HFCS、果糖、葡萄糖或阿斯巴甜的饮料时进行。这些研究的具体目的是验证以下假设，即2周的果糖或高果糖玉米糖浆摄入会增加DNL衍生的脂肪酸对深夜TRL升高的绝对贡献和比例贡献，并且DNL脂肪酸的增加将是空腹LDL和ApoB浓度升高的关键决定因素。第二个目标是确定高果糖玉米糖浆的剂量会增加dnl脂肪酸对餐后TRL的绝对贡献和比例贡献。公共卫生相关性：有证据表明，高糖饮食的消耗与心血管疾病和糖尿病的发病率增加有关，并且来自母体研究的早期结果表明，饮用含高果糖玉米糖浆（HFCS）的饮料（能量需求的25%）2周会增加心血管疾病的风险因素，包括深夜甘油三酯（TG）浓度、空腹低密度脂蛋白胆固醇和载脂蛋白b浓度。科学证据表明，餐后血浆TG浓度升高会导致其他危险因素的增加，因此建议研究HFCS和果糖摄入导致的深夜餐后TG升高的机制。这些研究将有助于确定糖的摄入如何增加心血管和相关代谢疾病的风险。（摘要结束）

DESCRIPTION (provided by applicant): The parent study for this proposed ancillary study is an NIH/NHLBI-funded investigation comparing the effects of consuming sweetened beverages for 2 weeks in young (18-40 years), normal weight and overweight/obese adults (5R01HL091333-02: Effects of 2wk fructose & HFCS consumption on lipid dysregulation & insulin resistance). Baseline experimental procedures (including 24-h serial blood sampling) are conducted while subjects reside as inpatients at the CTSC-funded Clinical Research Center (CCRC) for 3.5 days and consume an energy-balanced, high complex carbohydrate diet. Subjects then consume sweetened beverages providing 25% of energy requirements as fructose, glucose, or high fructose corn syrup (HFCS); or 0, 10, or 17.5% of energy as fructose or HFCS along with their usual ad libitum diet. At the end of the 2-week intervention, subjects return to the CCRC and the same experimental procedures are performed while subjects consume an energy-balanced diet, which includes the assigned sweetened beverages. The early results from this investigation indicate that consumption of HFCS-sweetened beverages at 25% of energy results in significant increases of late-night postprandial triglyceride (TG) concentrations, and of fasting LDL cholesterol and apolipoprotein-B (ApoB) concentrations that are comparable in magnitude to those observed after consumption of beverages sweetened with 100% fructose. Consumption of glucose-sweetened beverages does not alter these parameters. There is considerable evidence to support the hypothesis that postprandial hypertriglyceridemia is a key metabolic disturbance that gives rise to the lipid dysregulation characteristic of metabolic syndrome and type 2 diabetes. The purpose of this proposal is to investigate the mechanisms that contribute to the postprandial hypertriglyceridemia induced by fructose and HFCS consumption by quantifying the absolute and proportional contributions of fatty acids derived from de novo lipogenesis (DNL), diet, and free fatty acids (FFA) from adipose TG lipolysis to fasting and postprandial levels of triglyceride-rich lipoproteins (TRL). Stable isotopes will be administered (via oral consumption and 26-h intravenous infusions) to subsets of subjects during the 24-h serial blood sampling protocols that are conducted in all study participants during consumption of energy-balanced, high complex carbohydrate meals at baseline, and meals consumed with beverages sweetened with HFCS, fructose, glucose or aspartame at the end of intervention. The specific objective of these studies is to test the hypothesis that 2 weeks of fructose or HFCS consumption will increase the absolute and proportional contributions of fatty acids derived from DNL to late-night increases of TRL, and that the increases of DNL-fatty acid will be a critical determinant of the increases of fasting LDL and ApoB concentrations. A second objective is to determine the doses of HFCS that increase the absolute and proportional contributions of DNL-fatty acids to postprandial TRL. PUBLIC HEALTH RELEVANCE: There is evidence to suggest that consumption of high sugar diets is associated with increased incidence of cardiovascular disease and diabetes, and the early results from the parent study indicate that consumption of beverages sweetened with high fructose corn syrup (HFCS) at 25% of energy requirement for 2 weeks increases risk factors for cardiovascular disease, including late-night triglyceride (TG) concentrations, and fasting LDL-cholesterol and apolipoprotein-B concentrations. Scientific evidence suggests that increased plasma TG concentrations after meals lead to the increases of other risk factors, and studies are proposed to mechanistically investigate the late-night postprandial increase of TG induced by consumption of HFCS and fructose. These studies will help to determine how sugar consumption may promote increased risk for cardiovascular and related metabolic diseases. (End of Abstract)