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.

摘要 - 代谢和代谢健康（MMH）核心 对肥胖，糖尿病和相关病理生理学的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件的全面分析， 活动物中的大量营养素组合和代谢。将食物摄入与体重进行比较的简单测试 增益，或从单个静态条件中的代谢与代谢相关的分析物，无法完全捕获细微差别 生物能和代谢表型，进食行为的变化或身体成分的改变。 因此，已经设计和结构了新陈代谢和代谢健康（MMH）核心以提供 通过专家咨询，最先进的仪器和对评估的技术支持进行调查人员 小鼠 - 能量平衡，能量摄入（EI）和消化，能量消耗（EE），代谢效率，EI-EE 耦合表型，大量营养素代谢，骑马作用和分泌，身体/组织组成和 与微生物组和Xenometabolome的关联。 MMH核心将以服务为导向，面向客户端， 和研究支持。 MMH核心将由领导者，共同领导者，核心协调员，技术人员组成 专家和5位科学顾问。 MMH核心的任务将通过以下两个具体目标完成： 特定目的1：为客户提供创新和独特的资产以及深入的方法 表征与能量平衡，食物摄入，葡萄糖和甘油三酸酯有关的关键节点 现场代谢，代谢骑士敏感性，身体成分和肠道菌群代谢 老鼠。 特定目标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，肥胖和糖尿病领域的结果。 在这些特定目标下，MMH核心将进行以下活动： •对EI的急性，中和长期评估以及对EI调节激素的敏感性 雄性和雌性小鼠作为糖尿病，肥胖和其他代谢障碍的模型； •提供一系列生物能和EE测试，包括RER复杂模式和频率 分析，EE-EI耦合作为对能量平衡调节的测量和TNZ的表征 和TNP，包括极端温度，去甲肾上腺素，运动或定时餐 挑战； •通过Echomri和Piximus dexa进行人体组成分析以及研究 通过葡萄糖和胰岛素耐受性测试，连续葡萄糖监测，大量营养素代谢， 和肝甘油三酸酯的产生； •提供创新和独特的服务来评估微生物组和Xenometabolome， 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生成高质量和可重复的研究结果， 授予建议的试点数据和临床前发现，以告知人类临床试验； •灵活并响应用户对新的和可自定义的测定和过程的要求； •参加充满活力的计划，以协助和培训新一代科学家，并量身定制 专注于代表性不足的研究人员，并增加生物医学研究的多样性 通过以前与MMPC的关联，参与MMH核心的调查人员已经 在能源代谢，生物能，身体成分，葡萄糖研究研究中具有良好的专业知识和能力 活小鼠中的脂质稳态，食物摄入量，代谢组学和肠道菌群。与最先进的 UC Davis的ART设备，设施和核心分析实验室，MMH Core将是一个独特而高度的 有影响力的科学资产给对代谢生理感兴趣的国家研究人员和 糖尿病和肥胖。