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

• 批准号: 8487437
• 负责人: PETER J HAVEL
• 金额: $ 36.02万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-01 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8487437
• 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

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（由申请方提供）：本项拟议辅助研究的母研究是一项由NIH/NHLBI资助的研究，旨在比较年轻（18-40岁）、正常体重和超重/肥胖成人连续2周饮用含糖饮料的影响（5 R 01 HL 091333 -02：2周果糖和HFCS摄入对脂质失调和胰岛素抵抗的影响）。进行基线实验程序（包括24小时连续血液采样），同时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，并消耗能量平衡的高复合碳水化合物饮食。然后受试者食用加糖饮料，其提供25%的能量需求作为果糖、葡萄糖或高果糖玉米糖浆（HFCS）;或0、10或17.5%的能量作为果糖或HFCS沿着，以及他们通常的随意饮食。在2周干预结束时，受试者返回CCRC，并在受试者消耗能量平衡的饮食（包括指定的加糖饮料）的同时进行相同的实验程序。这项调查的早期结果表明，以25%的能量消耗HFCs甜味饮料会导致深夜餐后甘油三酯（TG）浓度以及空腹LDL胆固醇和载脂蛋白-B（ApoB）浓度的显著增加，其幅度与消耗100%果糖甜味饮料后观察到的结果相当。饮用含葡萄糖的饮料不会改变这些参数。有相当多的证据支持这一假设，即餐后高甘油三酯血症是一种关键的代谢紊乱，引起代谢综合征和2型糖尿病的脂质失调特征。本提案的目的是通过量化源自从头脂肪生成（DNL）、饮食和脂肪TG脂解的游离脂肪酸（FFA）对空腹和餐后富含果糖的脂蛋白（TRL）水平的绝对和比例贡献，研究果糖和HFCS消耗诱导的餐后高甘油三酯血症的机制。在24小时连续血液采样方案期间，将向受试者亚组给予稳定同位素（通过口服和26小时静脉输注），该方案在基线时能量平衡的高复合碳水化合物膳食消费期间以及干预结束时与HFCS、果糖、葡萄糖或甜化饮料一起消费的膳食中对所有研究参与者进行。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脂肪酸的增加将是空腹LDL和ApoB浓度增加的关键决定因素。第二个目的是确定增加DNL-脂肪酸对餐后TRL的绝对和比例贡献的HFCS剂量。