Weight-Loss Diet Intervention on Cardiometabolic Factors of Gut Microbiota

减肥饮食对肠道菌群心脏代谢因素的干预

• 批准号: 9535815
• 负责人: Lu Qi
• 金额: $ 32.22万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-15 至 2020-03-09
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9535815
• 关键词: Address; Adipose tissue; Affect; Amino Acids; Basal metabolic rate; Bile Acids; Blood; Blood specimen; Body Weight decreased; Body measure procedure; Carbohydrates; Cardiovascular Diseases; Clinical Trials; Collection; Desire for food; Diabetes Mellitus; Diet; Dietary Factors; Dietary Intervention; Energy Intake; Energy Metabolism; Epidemiology; Fatty acid glycerol esters; Funding; Gene Expression; Gene Expression Profiling; Genetic Transcription; Glycine; Goals; Grant; Health; Hormones; Human; Inflammation; Insulin Resistance; Leptin; Levocarnitine; Link; Lipids; Long-Term Effects; Longitudinal Studies; Macronutrients Nutrition; Measurement; Measures; Mediating; Metabolic; Metabolic Diseases; Metabolic Marker; Metabolism; Methods; Molecular; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Organ; Overweight; Participant; Patients; Pattern; Plasma; Play; Prevention strategy; Proteins; Qi; RBP4 gene; Resources; Risk Factors; Role; Sampling; Shapes; Solid; Taurine; United States National Institutes of Health; adipokines; adiponectin; cost efficient; doubly-labeled water; energy balance; experience; ghrelin; glucagon-like peptide 1; gut microbiota; inflammatory marker; innovation; insight; insulin sensitivity; metabolomics; novel; nutrition; obesity prevention; proctolin; prospective; public health relevance; randomized trial; statistics; total energy expenditure; treatment strategy; trimethyloxamine

DESCRIPTION (provided by applicant): Gut microbiota has recently emerged as a novel, metabolically active 'organ', tightly linked to obesity and related metabolic disorders such as diabetes and cardiovascular disease; and compelling evidence indicates that several key metabolites (TMAO, L-carnitine, bile acids subtypes) related to gut microbiota metabolism may play pivotal roles in mediating the metabolic effects. Diet is a major force that shapes gut microbiota and weight loss may alter metabolism of gut microbiota. The goal of this application is to examine the long-term (2 years) effects of weight-loss diets varying in macronutrients (fat, protein, and carbohydrate) on the novel cardiometabolic metabolites involved in gut microbiota metabolism in 811 overweight or obese patients from thus far one of the largest and most comprehensive comparator trials on the popular weight-loss diets - the POUNDS LOST trial. We will also assess the relation of changes in plasma gut microbiota metabolites with changes in markers of energy intake and expenditure, including gut hormones (GLP-1, ghrelin), resting metabolic rate (RMR), and total energy expenditure (TEE) measured by doubly-labeled water (DLW); as well as with changes in metabolic risk factors including insulin sensitivity, lipids, adipokines, inflammation, and amino acids. In addition, we will examine the associations between gut microbiota metabolites and global adipose gene expression. Because measurement of energy balance and metabolic markers, and adipose gene expression are funded through separate grants, the proposed project will be conducted in an extremely cost-efficient manner. We have assembled a solid group of experienced collaborators with expertise in epidemiology, metabolomics, gene expression, statistics, clinical trial, and nutrition. We believe that findings of this project will provide novel insights into the metabolic effects of gut microbiota and their relations with dietary factors; and considerably contribute to advance toward new prevention and treatment strategies for obesity and related metabolic disorders through diet intervention.

描述（由申请人提供）：肠道微生物群最近已成为一种新型的、代谢活跃的“器官”，与肥胖和相关代谢紊乱（如糖尿病和心血管疾病）密切相关；令人信服的证据表明，与肠道微生物群代谢相关的几种关键代谢物（TMAO、左旋肉碱、胆汁酸亚型）可能在介导代谢效应中发挥关键作用。饮食是塑造肠道微生物群的主要力量，减肥可能会改变肠道微生物群的新陈代谢。本申请的目的是通过迄今为止最大、最全面的流行减肥饮食比较试验之一——POUNDS LOST 试验，研究 811 名超重或肥胖患者的常量营养素（脂肪、蛋白质和碳水化合物）不同的减肥饮食对参与肠道微生物群代谢的新型心脏代谢代谢物的长期（2 年）影响。我们还将评估血浆肠道微生物代谢物的变化与能量摄入和消耗标志物变化的关系，包括肠道激素（GLP-1、生长素释放肽）、静息代谢率（RMR）和通过双标记水（DLW）测量的总能量消耗（TEE）；以及代谢危险因素的变化，包括胰岛素敏感性、血脂、脂肪因子、炎症和氨基酸。此外，我们将研究肠道微生物代谢物与整体脂肪基因表达之间的关联。由于能量平衡和代谢标记物以及脂肪基因表达的测量是通过单独的赠款资助的，因此拟议的项目将以极具成本效益的方式进行。我们聚集了一批经验丰富的合作者，他们在流行病学、代谢组学、基因表达、统计学、临床试验和营养方面拥有专业知识。我们相信该项目的研究结果将为肠道代谢影响提供新的见解 微生物群及其与饮食因素的关系；并通过饮食干预为肥胖和相关代谢紊乱的新预防和治疗策略做出巨大贡献。