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）：过去几十年预示着高碳水化合物（CHO）饮食的时代，其中一些饮食现在已知会使脂质谱恶化并增加心血管疾病（CVD）的风险。日粮组成和进食频率都影响脂质合成和动力学，但具体机制尚不清楚。我们将验证CHO向脂肪的转化（从头脂肪生成[DNL]）是餐后甘油三酯（TG）和脂蛋白通量的主要决定因素，导致血清TG水平升高和血脂异常。我们建议进行对照代谢研究，利用饮食组成和进餐频率来调节餐后DNL，并评估其对TG和载脂蛋白（apo） B通量、脂质谱和脂蛋白颗粒分布的影响。我们将通过测量超重和肥胖志愿者中极低密度脂蛋白（VLDL，来自肝脏）和乳糜微粒（乳糜，来自肠道）对总体餐后脂蛋白- tg产生和清除的个体贡献来做到这一点，超重和肥胖志愿者是有心血管疾病风险的人群。我们将使用稳定同位素示踪剂和复杂的数学模型，比较饲喂高糖或高脂两种等热量饲料（随机分配）7天对餐后DNL、VLDL-TG和乳糜- tg以及载脂蛋白B100和B48通量的影响。采用随机交叉设计将参与者分配到每种饮食中，我们还将比较连续7天少食多餐（一点点）和每天进食2餐之间的差异程度，每个参与者都是他/她自己的对照组。参与者将被安置在代谢病房，并持续喂食维持体重的饮食，以确保饮食的坚持和控制活动。肝脏脂质储存将通过磁共振（MR）光谱测量，内脏脂肪通过磁共振成像测量，瘦肉和脂肪质量通过双能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风险联系起来，将使用专有的HPLC方法和凝胶电泳测量VLDL和乳糜残留物的组成、脂蛋白颗粒大小、小密度低密度脂蛋白和高密度脂蛋白。我们期望这些新颖的研究将使我们首次确定膳食成分和频率影响餐后载脂蛋白和TG通量以及相关脂质谱的机制。这些发现可以为制定以证据为基础的干预措施和饮食指导提供信息，以降低心血管疾病的风险。