Metabolism and Metabolic Health Core

新陈代谢和代谢健康核心

• 批准号: 10588974
• 负责人: Sean Harrison Adams
• 金额: $ 18.27万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-02-01 至 2028-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10588974
• 关键词: Acute; Address; Animals; Applications Grants; Area; Behavior; Bioenergetics; Biological Assay; Biomedical Research; Body Composition; Catalogs; Client; Clinical Trials; Collaborations; Complement; Complex; Consultations; Continuous Glucose Monitor; Core Assembly; Coupled; Coupling; Data; Data Set; Diabetes Mellitus; Digestion; Dual-Energy X-Ray Absorptiometry; Eating; Energy Intake; Energy Metabolism; Equipment; Exercise; Feeding behaviors; Female; Frequencies; Functional disorder; Generations; Glucose; Goals; Health; Hepatic; Homeostasis; Hormones; Human; Infrastructure; Institution; Link; Lipids; Macronutrients Nutrition; Measures; Metabolic; Metabolic Diseases; Metabolic dysfunction; Metabolic hormone; Metabolism; Methods; Mission; Modeling; Molecular; Mus; Norepinephrine; Obesity; Outcome; Participant; Pattern; Phenotype; Physiology; Play; Procedures; Production; Publications; Regulation; Reproducibility; Research; Research Design; Research Personnel; Role; Scientist; Services; Signal Transduction; Specialist; Structure; Techniques; Testing; Tissues; Training; Triglyceride Metabolism; Triglycerides; Weight Gain; Work; complex data; design; energy balance; experience; experimental study; extreme temperature; feeding; flexibility; frontier; glucose metabolism; glucose tolerance; gut microbiome; gut microbiota; hormone sensitivity; in vivo; innovation; instrumentation; insulin tolerance; interest; male; metabolic phenotype; metabolomics; microbiome; mouse model; pre-clinical; programs; whole body imaging

ABSTRACT—METABOLISM AND METABOLIC HEALTH (MMH) CORE Investigators interested in mechanisms underlying the pathophysiology of obesity, diabetes and related metabolic diseases will benefit from a comprehensive analysis of components regulating energy balance, macronutrient combustion and metabolism in live animals. Simple tests that compare food intake to weight gain, or that measure metabolically-relevant analytes from a single static condition, fail to fully capture nuanced bioenergetic and metabolic phenotypes, changes in feeding behaviors, or alterations of body composition. Therefore, the Metabolism and Metabolic Health (MMH) Core has been designed and structured to provide investigators with expert consultation, state-of-the-art instrumentation, and technical support to assess—in live mice—energy balance, energy intake (EI) and digestion, energy expenditure (EE), metabolic efficiency, EI-EE coupling phenotypes, macronutrient metabolism, hormone action and secretion, body/tissue composition, and associations with the microbiome and xenometabolome. The MMH Core will be service-oriented, client-facing, and research-supportive. The MMH Core will be staffed by a Leader, co-Leader, Core Coordinator, Technical Specialists, and 5 Scientific Consultants. The mission of the MMH Core will be accomplished through the following 2 Specific Aims: Specific Aim 1: Provide clients with innovative and unique assets and approaches to deeply- characterize key nodes involved with energy balance, food intake, glucose and triglyceride metabolism, metabolic hormone sensitivity, body composition and gut microbiota metabolism in live mice. Specific Aim 2: Provide clients with consultation services focused on study design and interpretation of results in the areas of metabolic physiology, obesity, and diabetes. Under these specific aims, the MMH Core will carry out the following activities: • Providing acute, mid, and long -term assessments of EI and sensitivity to EI-regulating hormones in male and female mice as models of diabetes, obesity, and other metabolic disorders; • Offering a battery of bioenergetics and EE tests, including RER complex pattern and frequency analysis, EE-EI coupling as a measure of energy balance regulation, and characterization of TNZ and TNP, including under temperature extremes, norepinephrine, exercise, or timed meal challenges; • Conducting analyses of body composition by EchoMRI and PixiMus DEXA and studies of macronutrient metabolism via glucose and insulin tolerance tests, continuous glucose monitoring, and hepatic triglyceride production; • Providing innovative and unique services to assess the microbiome and xenometabolome, metabolic and feeding efficiency, and whole-body imaging to complement services obtained from the PB Core; • Assisting investigators to generate high-quality and reproducible research results for publications, pilot data for grant proposals, and preclinical findings to inform human clinical trials; • Being flexible and responsive to user requests for new and customizable assays and procedures; • Participating in the Vibrant Program to assist and train a new generation of scientists with a tailored focus toward underrepresented investigators and increasing diversity in biomedical research Through their previous association with the MMPC, the investigators participating in the MMH Core have proven expertise and capabilities in the study of energy metabolism, bioenergetics, body composition, glucose and lipid homeostasis, food intake, metabolomics, and gut microbiota in live mice. When coupled with state-of- the-art equipment, facilities, and core analytical labs at UC Davis, the MMH Core will be a unique and highly- impactful scientific asset to national investigators interested in metabolic physiology and the pathophysiology of diabetes and obesity.

代谢和代谢健康（MMH）核心 对肥胖、糖尿病及相关疾病的病理生理学机制感兴趣的研究者 代谢疾病将受益于调节能量平衡的组分的综合分析， 活动物体内大量营养素的燃烧和代谢。比较食物摄入量和体重的简单测试 增益或从单一静态条件测量代谢相关分析物，不能完全捕获细微差别 生物能量和代谢表型、摄食行为的变化或身体组成的改变。 因此，代谢和代谢健康（MMH）核心的设计和结构， 研究人员提供专家咨询、最先进的仪器和技术支持，以进行现场评估 小鼠能量平衡，能量摄入和消化，能量消耗，代谢效率 偶联表型、常量营养素代谢、激素作用和分泌、身体/组织组成，以及 与微生物组和异种代谢组的关联。MMH核心将面向服务，面向客户， 和研究支持。MMH核心将配备一名领导人、共同领导人、核心协调员、技术 专家和5名科学顾问。 MMH核心的使命将通过以下2个具体目标来实现： 具体目标1：为客户提供创新和独特的资产和方法， 表征涉及能量平衡、食物摄入、葡萄糖和甘油三酯的关键节点 肝脏代谢、代谢激素敏感性、身体组成和肠道微生物群代谢 小鼠 具体目标2：为客户提供专注于研究设计和解释的咨询服务 代谢生理学、肥胖症和糖尿病领域的研究成果。 根据这些具体目标，产妇保健核心方案将开展以下活动： ·提供急性、中期和长期的EI评估以及对EI调节激素的敏感性， 雄性和雌性小鼠作为糖尿病、肥胖症和其他代谢紊乱的模型; ·提供一系列生物能量学和EE测试，包括RER复杂模式和频率 分析，EE-EI耦合作为能量平衡调节的测量，以及TNZ的表征 和TNP，包括在极端温度下，去甲肾上腺素，运动或定时进餐 挑战; ·通过EchoMRI和PixiMus DEXA进行身体成分分析， 通过葡萄糖和胰岛素耐量试验的大量营养素代谢，连续葡萄糖监测， 和肝甘油三酯生成; ·提供创新和独特的服务，以评估微生物组和异种代谢组， 代谢和喂养效率，以及全身成像，以补充从 PB核心; ·协助研究人员为出版物产生高质量和可重复的研究结果， 用于资助提案的试点数据，以及为人类临床试验提供信息的临床前发现; ·灵活并响应用户对新的和可定制的测定和程序的请求; ·参与充满活力的计划，以帮助和培训新一代的科学家， 关注代表性不足的研究者和生物医学研究的日益多样化 通过他们以前与MMPC的联系，参与MMH核心的研究者已经 在研究能量代谢、生物能量学、身体成分、葡萄糖 和脂质稳态、食物摄入、代谢组学和肠道微生物群。当与国家的， 先进的设备，设施和核心分析实验室在加州大学戴维斯分校，MMH核心将是一个独特的，高度- 为对代谢生理学和疾病病理生理学感兴趣的国家研究人员提供有影响力的科学资产。 糖尿病和肥胖症。