Fatty acid sources of fructose and HFCS-induced postprandial hypertriglyceridemia

果糖的脂肪酸来源和 HFCS 诱发的餐后高甘油三酯血症

基本信息

批准号：
8680329
负责人：
PETER J HAVEL
金额：
$ 35.56万
依托单位：
UNIVERSITY OF CALIFORNIA AT DAVIS
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-09-01 至 2017-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8680329
关键词：
Adipose tissue Adult Ancillary Study Apolipoproteins B Aspartame Blood specimen Carbohydrates Cardiovascular Diseases Characteristics Clinical Research Complex Consumption Data Development Diabetes Mellitus Diet Dietary Intervention Dose Epidemiology Fasting Fatty Acids Fructose Funding Glucose Hour Hypertriglyceridemia Incidence Inpatients Insulin Resistance Intake Intervention Intravenous infusion procedures Investigation LDL Cholesterol Lipoproteins Lead Link Lipids Lipolysis Lipoproteins Low-Density Lipoproteins Measurement Metabolic Metabolic Diseases Metabolic syndrome Methodology National Heart, Lung, and Blood Institute Non-Insulin-Dependent Diabetes Mellitus Nonesterified Fatty Acids Obesity Oral Overweight Parents Participant Plasma Procedures Production Protocols documentation Regimen Risk Factors Source Testing Tracer Triglycerides United States National Institutes of Health Weight abstracting cardiovascular risk factor energy balance feeding insight lipid biosynthesis novel stable isotope sugar sweetened beverage young man young woman

项目摘要

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.

描述（由申请人提供）：这项拟议辅助研究的母研究是一项由 NIH/NHLBI 资助的调查，比较了年轻人（18-40 岁）、正常体重和超重/肥胖成年人饮用甜味饮料 2 周的影响（ 5R01HL091333-02：2 周果糖和 HFCS 消耗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）是在受试者在 CTSC 资助的临床研究中心 (CCRC) 住院 3.5 天并摄入能量平衡的高复合碳水化合物饮食时进行的。然后受试者饮用可提供 25% 能量需求的甜味饮料，如果糖、葡萄糖或高果糖玉米糖浆 (HFCS)；或者 0、10 或 17.5% 的能量作为果糖或 HFCS 以及他们通常的随意饮食。两周干预结束后，受试者返回 CCRC，并进行相同的实验程序，同时受试者食用能量平衡饮食，其中包括指定的甜饮料。这项调查的早期结果表明，饮用 25% 能量的 HFCS 含糖饮料会导致深夜餐后甘油三酯 (TG) 浓度显着增加，并且空腹 LDL 胆固醇和载脂蛋白 B (ApoB) 浓度显着增加，与与饮用 100% 果糖甜味饮料后观察到的结果相当。饮用葡萄糖饮料不会改变这些参数。有大量证据支持这一假设，即餐后高甘油三酯血症是一种关键的代谢紊乱，导致代谢综合征和 2 型糖尿病的脂质失调特征。该提案的目的是通过量化从头脂肪生成 (DNL)、饮食和游离脂肪酸 (FFA) 衍生的脂肪酸的绝对和比例贡献，研究果糖和 HFCS 摄入引起的餐后高甘油三酯血症的机制从脂肪 TG 脂解到空腹和餐后富含甘油三酯的脂蛋白 (TRL) 水平。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）给予受试者子集，所有研究参与者在基线时食用能量平衡的高复合碳水化合物膳食期间进行该方案，以及在干预结束时与含 HFCS、果糖、葡萄糖或阿斯巴甜的甜味饮料一起食用。这些研究的具体目的是检验以下假设：2 周的果糖或 HFCS 摄入将增加 DNL 衍生的脂肪酸对深夜 TRL 增加的绝对和比例贡献，并且 DNL 脂肪酸的增加将增加是空腹 LDL 和 ApoB 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。