Lipogenesis, lipoprotein flux & CVD risk: role of meal composition & frequency

脂肪生成、脂蛋白通量

• 批准号: 8438137
• 负责人: Kathleen Mulligan
• 金额: $ 62.36万
• 依托单位: TOURO UNIVERSITY OF CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-06-01 至 2018-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8438137
• 关键词: Adherence; Affect; Apolipoproteins; Apolipoproteins B; Carbohydrates; Cardiovascular Diseases; Chylomicrons; Consumption; Crossover Design; Data; Diet; Diet Fads; Dietary Fats; Dietary Sugars; Dual-Energy X-Ray Absorptiometry; Dyslipidemias; Evidence based intervention; Fasting; Fatty acid glycerol esters; Frequencies; Fructose; Health Policy; Hepatic; High Density Lipoproteins; High Pressure Liquid Chromatography; Housing; Hyperlipidemia; Image; Individual; Ingestion; Intake; Intestines; Kinetics; Lead; Link; Lipids; Lipoproteins; Liver; Liver diseases; Low-Density Lipoproteins; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Measures; Metabolic; Metabolic Clearance Rate; Metabolism; Methods; Minor; Modeling; Nutrient; Obesity; Outcome Study; Overweight; Participant; Particle Size; Pattern; Physiological; Plasma; Population; Production; Public Health; Randomized; Recommendation; Risk; Risk Factors; Role; Serum; Source; Sucrose; Techniques; Testing; Time; Tracer; Triglycerides; Very low density lipoprotein; Visceral; Weight; apolipoprotein B-48; base; cardiovascular disorder risk; energy balance; evidence base; feeding; gel electrophoresis; lipid biosynthesis; lipoprotein triglyceride; mathematical model; metabolic abnormality assessment; non-alcoholic fatty liver; novel; particle; public health relevance; response; stable isotope; sugar; translational study; very low density lipoprotein triglyceride; volunteer; ward

DESCRIPTION (provided by applicant): The past few decades heralded an era of high carbohydrate (CHO) diets, some of which are now known to worsen lipid profiles and increase risk of cardiovascular disease (CVD). Both diet composition and meal frequency affect lipid synthesis and kinetics, but the specific mechanisms remain unsettled. We will test the hypothesis that the conversion of CHO to fat (de novo lipogenesis [DNL]) is a major determinant of postprandial triglyceride (TG) and lipoprotein fluxes leading to higher levels of serum TG and dyslipidemia. We propose to perform controlled metabolic studies that use diet composition and meal frequency to modulate postprandial DNL and assess its impact on TG and apolipoprotein (apo) B fluxes, lipid profiles and lipoprotein particle distribution. We will do so by measuring th individual contributions of very low density lipoprotein (VLDL; from the liver) and chylomicrons (chylos, from the intestine) to overall postprandial lipoprotein-TG production and clearance in overweight and obese volunteers, a population that is at risk for CVD. We will compare the effects of 7 days feeding with two isocaloric diets (randomly assigned) that are either high in sucrose or high in fat on postprandial DNL, VLDL-TG and chylo-TG, and apolipoprotein B100 and B48 fluxes using stable isotope tracers and sophisticated mathematical modeling. Using a randomized crossover design in participants assigned to each diet, we will also compare the magnitude of differences between successive 7-day periods of consuming small frequent meals (nibbling) and ingesting 2 daily meals, with each participant serving as his/her own control. Participants will be housed in a metabolic ward and fed constant weight-maintaining diets to assure dietary adherence and control activity. Liver lipid storage will be measured by magnetic resonance (MR) spectroscopy, visceral fat by MR imaging, and lean and fat mass by dual energy X-ray absorptiometry. To further link the dynamic fluxes to atherogenic risk, the composition of VLDL and chylo remnants, lipoprotein particle sizes, small dense low density lipoprotein and high density lipoprotein will be measured using proprietary HPLC methods and gel electrophoresis. We anticipate that these novel studies will allow us to identify, for the firs time, the mechanisms by which meal composition and frequency affect postprandial apoB and TG fluxes and associated lipid profiles. These findings could inform efforts to develop evidence-based interventions and dietary guidance to mitigate CVD risk.

描述（由申请人提供）：过去几十年来预示了高碳水化合物（CHO）饮食的时代，其中一些饮食现在已知会使脂质概况恶化并增加心血管疾病（CVD）的风险。饮食成分和粉状频率都会影响脂质合成和动力学，但具体机制仍未解决。我们将检验以下假设：CHO向脂肪的转化（从头脂肪生成[DNL]）是餐后甘油三酸酯（TG）和脂蛋白通量的主要决定因素，导致血清TG和血脂症水平较高。我们建议进行控制的代谢研究，以使用饮食组成和粉状频率调节餐后DNL，并评估其对TG和载脂蛋白（APO）B通量，脂质谱，脂质谱和脂蛋白颗粒分布的影响。我们将通过测量非常低密度脂蛋白（VLDL；来自肝脏）和胆小性（从肠道，肠道）对餐后脂蛋白-TG产生和肥胖志愿者的清除的个人贡献，这是一种有CVD的风险。我们将与两种蔗糖（随机分配）的7天喂养作用进行比较，这些饮食含量很高，它们对餐后DNL，VLDL-TG和Chylo-TG的含量高或脂肪含量高，以及使用稳定的同位素示踪剂和apolipopolotein b100和apolipopolotein B100和B48磁通量。在分配给每种饮食的参与者中，我们还将比较连续7天的饮食量频繁餐点（nibbling）和每天摄入2顿饭之间的差异的程度，每个参与者都作为自己的控制。参与者将被安置在代谢病房中，并喂养持续的减肥饮食，以确保饮食依从性和控制活动。肝脂质储存将通过磁共振（MR）光谱，MR成像的内脏脂肪以及双能X射线吸收仪测量。为了进一步将动态通量与动脉粥样硬化的风险联系起来，将使用专有的HPLC方法和凝胶电泳测量VLDL和CHYLO残留物，脂蛋白颗粒尺寸，脂蛋白颗粒尺寸，小密集的低密度脂蛋白和高密度脂蛋白。我们预计这些新型研究将使我们能够在FIR时间识别餐食组成和频率影响餐后APOB和TG通量以及相关脂质谱的机制。这些发现可以为制定基于证据的干预措施和饮食指导以减轻CVD风险的努力。