Fatty acid sources of fructose and HFCS-induced postprandial hypertriglyceridemia

描述(申请人提供)：这项拟议的辅助研究的家长研究是由NIH/NHLBI资助的一项研究，比较了年轻人(18-40岁)、正常体重和超重/肥胖成年人饮用两周含糖饮料的效果(5R01HL091333-02：摄入2wk果糖和HFCS对血脂失调和胰岛素抵抗的影响)。当受试者作为住院患者在CTSC资助的临床研究中心(CCRC)居住3.5天，并食用能量平衡的高复合碳水化合物饮食时，进行基线实验程序(包括24小时连续采血)。然后，受试者在日常随意饮食的同时，饮用提供25%能量需求的含糖饮料，如果糖、葡萄糖或高果糖玉米糖浆(HFCS)；或提供0、10%或17.5%的能量需求，如果糖或高果糖玉米糖浆。在为期两周的干预结束后，受试者回到CCRC，进行同样的实验程序，同时受试者摄入能量平衡的饮食，其中包括分配的含糖饮料。这项调查的早期结果表明，以25%的能量摄入HFCS含糖饮料会显著增加深夜餐后甘油三酯(TG)浓度，以及空腹低密度脂蛋白胆固醇和载脂蛋白B(ApoB)浓度，其幅度与饮用100%果糖含糖饮料后观察到的水平相当。饮用含糖饮料不会改变这些参数。有相当多的证据支持这一假说，即餐后高甘油三酯血症是导致代谢综合征和2型糖尿病所特有的脂代谢紊乱的关键代谢紊乱。这项建议的目的是通过量化来自新生脂肪生成(DNL)的脂肪酸、饮食和来自脂肪甘油三酯脂解的游离脂肪酸(FFA)对富含甘油三酯的脂蛋白(TRL)的空腹和餐后水平的绝对和比例贡献，来研究由果糖和HFCS摄入引起的餐后高甘油三酯血症的机制。在对所有研究参与者进行24小时系列血液采样期间，将对受试者的不同亚组进行稳定同位素的注射(通过口服和26小时静脉输注)，在干预结束时，在摄入能量平衡的高复杂碳水化合物膳食，以及在干预结束时食用含HFCS、果糖、葡萄糖或阿斯巴甜的饮料。这些研究的具体目的是检验这样一种假设，即2周的果糖或HFCS摄入将增加来自DNL的脂肪酸对深夜TRL增加的绝对和比例贡献，以及DNL-脂肪酸的增加将是空腹低密度脂蛋白和载脂蛋白B浓度增加的关键决定因素。第二个目标是确定增加DNL-脂肪酸对餐后TRL的绝对和比例贡献的HFCS剂量。

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.