Washington University Nutrition Obesity Research Center

项目摘要/摘要--概述： 这项申请寻求继续为华盛顿大学医学院(WUSM)营养提供资金 肥胖研究中心(NORC)自从我们的NORC于1999年首次获得资金以来，它一直是 WUSM营养与肥胖研究的成长与发展。NORC提供的基础设施 创造了一种支持和刺激具有成本效益的高质量研究的环境， 研究人员之间的合作，职业发展和培训，以及营养和临床活动 肥胖。我们的NORC拥有一个才华横溢和多样化的研究基地，由来自19个国家的109名调查人员组成 各部门。这些研究人员有179笔与营养/肥胖有关的赠款，每年产生4200万美元 直接成本。我们打算继续发展与营养和肥胖相关的活动，并继续 将最先进的基础和临床研究方法带给NORC的调查人员。总体研究重点 WUSM NORC的主要问题是：1)肥胖：病理生理学、并发症和治疗；2)营养 健康和疾病中的新陈代谢；以及3)生长、发育和衰老。新兴的重大领域 兴趣包括：4)肠道微生物组和5)社区健康。我们提出了管理核心和4 生物医学研究核心。临床科学研究中心将在以下方面提供援助：i)学科 征聘、设计和执行复杂的代谢研究，二)身体成分评估，三) 静脉示踪剂和激素溶液的混合，iv)组织(脂肪、肌肉、肠道)的采集 样本，五)锻炼(耐力和力量)和体能测试，六)生活方式(饮食 操作、减肥和锻炼)干预，vii)进食行为(味觉和偏好) )心血管评估(例如，超声心动图、内皮功能、颈动脉内膜中层 厚度)；ix)测量血液和组织样品中代谢底物的稳定同位素丰度， 以及x)示踪剂和非示踪剂数据的数学模型，以评估代谢动力学和细胞功能。 动物模型研究核心将使用与以下相关的小鼠模型为研究人员提供服务 营养，包括：一)维持转基因小鼠的繁育群体；二)训练繁殖和 畜牧业，三)血液和组织样本的生化和分子分析，三)身体成分 分析、iv)基因分型和v)代谢表型。生物分子分析核心将提供 允许对血液和组织中与营养相关的生物分子进行结构识别和定量的服务 样本。脂肪细胞生物学和分子营养核心将提供脂肪组织形态， 脂肪细胞和肌肉细胞系用于培养、基因和蛋白质表达、线粒体生理学和训练 在专门的研究技术方面。我们的NORC研究之间的协作和协同关系 基地和我们的四个核心实验室将通过促进团队科学来正规化，以进一步鼓励 采用跨学科方法解决营养和肥胖方面的重要问题。此外，NORC将 每年资助4个试点和可行性奖给初级教员，并帮助指导他们。

PROJECT SUMMARY/ABSTRACT – Overview: This application seeks continued funding for the Washington University School of Medicine (WUSM) Nutrition Obesity Research Center (NORC). Since our NORC was first funded in 1999, it has served as a nidus for the growth and development of nutrition and obesity research at WUSM. The infrastructure provided by the NORC has created an environment that supports and stimulates cost-effective and high-quality research, collaborations between investigators, career development and training, and clinical activities in nutrition and obesity. Our NORC has a talented and diverse research base consisting of 109 investigators from 19 departments. These investigators have 179 nutrition/obesity-related grants, generating $42 million/year in direct costs. It is our intention to continue to grow nutrition and obesity-related activities, and to continue to bring state-of-the-art basic and clinical research methods to NORC investigators. The overall research focus of the WUSM NORC has been: 1) Obesity: Pathophysiology, Complications and Therapeutics; 2) Nutrient Metabolism in Health and Disease; and 3) Growth, Development, and Aging. Newly emerging areas of major interest include: 4) Gut Microbiome and 5) Community Health. We propose an Administrative Core and 4 Biomedical Research Cores. The Clinical Science Research Core will provide assistance with: i) subject recruitment, design and performance of complex metabolic studies, ii) body composition assessments, iii) mixing of intravenous tracers and hormone solutions, iv) acquisition of tissue (adipose, muscle, intestine) samples, v) exercise (endurance and strength) and physical performance testing, vi) lifestyle (diet manipulation, weight loss and exercise) interventions, vii) ingestive behavior (taste perception and preference) testing, viii) cardiovascular assessments (e.g., echocardiography, endothelial function, carotid intima-media thickness); ix) measurement of stable isotope enrichment of metabolic substrates in blood and tissue samples, and x) mathematical modeling of tracer and non-tracer data to assess metabolic kinetics and -cell function. The Animal Model Research Core will provide services to investigators using murine models relevant to nutrition, including: i) maintaining breeding colonies of genetically modified mice, ii) training in breeding and animal husbandry, iii) biochemical and molecular analyses of blood and tissue samples, iii) body composition analyses, iv) genotyping, and v) metabolic phenotyping. The Biomolecular Analyses Core will provide services to permit structural identification and quantitation of nutrition-related biomolecules in blood and tissue samples. The Adipocyte Biology and Molecular Nutrition Core will provide adipose tissue morphology, adipocyte and muscle cell lines for culture, gene and protein expression, mitochondrial physiology, and training in specialized research techniques. The collaborative and synergistic relationships among our NORC research base and our four Core laboratories will be formalized by promoting “team science” to further encourage interdisciplinary approaches to address important issues in nutrition and obesity. In addition, the NORC will fund 4 Pilot & Feasibility Awards/year to junior faculty and help mentor them.