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(申请人提供)：过去几十年预示着高碳水化合物(CHO)饮食时代的到来，其中一些现在已知会恶化血脂状况并增加心血管疾病(CVD)的风险。饮食结构和进餐频率都影响脂肪合成和动力学，但具体机制尚不清楚。我们将检验这一假设，即CHO向脂肪的转化(从头脂肪生成[DNL])是餐后甘油三酯(TG)和脂蛋白流动的主要决定因素，从而导致血清TG水平和血脂异常。我们建议进行受控代谢研究，使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、血脂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)和乳糜粒(来自肠道)对整体餐后脂蛋白-TG产生和清除的个体贡献来实现这一点，而超重和肥胖志愿者是心血管疾病的高危人群。我们将使用稳定的同位素示踪剂和复杂的数学模型，比较两种高蔗糖或高脂肪等热量饮食(随机分配)7天对餐后DNL、VLDL-TG和Chylo-TG以及载脂蛋白B100和B48通量的影响。在分配给每种饮食的参与者中使用随机交叉设计，我们还将比较连续7天的少量频繁进食(小口咀嚼)和每天摄入2顿饭之间的差异，每个参与者作为自己的对照。参与者将被安置在新陈代谢病房，并喂食持续的体重维持饮食，以确保饮食坚持和控制活动。肝脏脂肪储存将通过磁共振(MR)光谱进行测量，内脏脂肪将通过MR成像进行测量，而瘦肉和脂肪质量将通过双能X射线吸收法进行测量。为了进一步将动态流量与动脉粥样硬化的风险联系起来，将使用专有的高效液相方法和凝胶电泳法测量极低密度脂蛋白和乳胶残留物的组成、脂蛋白颗粒大小、小而致密的低密度脂蛋白和高密度脂蛋白。我们预计，这些新颖的研究将使我们能够首次确定膳食成分和频率影响餐后载脂蛋白B和甘油三酯流量以及相关血脂谱的机制。这些发现可以为开发循证干预和饮食指导以降低心血管疾病风险的努力提供参考。