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.

新陈代谢与代谢健康(MMH)核心 研究人员对肥胖、糖尿病及相关疾病的病理生理学机制感兴趣 代谢性疾病将受益于对调节能量平衡的组成部分的全面分析， 常量营养素在活体动物体内的燃烧和代谢。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与代谢相关分析物，不能完全捕捉细微差别 生物能量和代谢表型、摄食行为的改变或身体成分的改变。 因此，代谢和新陈代谢健康(MMH)核心的设计和结构提供了 为调查人员提供专家咨询、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(EI)和消化，能量消耗(EE)，代谢效率，EI-EE 偶联表型，大量营养素代谢，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系。MMH的核心将是面向服务的、面向客户的 和研究支持。MMH核心将由一名领导、联合领导、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两个具体目标来完成： 具体目标1：为客户提供创新和独特的资产和方法，以深入- 描述与能量平衡、食物摄入量、葡萄糖和甘油三酯有关的关键节点 活体代谢、代谢激素敏感性、体成分和肠道微生物区系代谢 老鼠。 具体目标2：为客户提供以研究设计和解释为重点的咨询服务 在代谢生理学、肥胖症和糖尿病领域的结果。 根据这些具体目标，MMH核心将开展以下活动： ·提供对EI的急性、中期和长期评估以及对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复合模式和频率 分析，EE-EI耦合作为能量平衡调节的一种手段，以及TNZ的表征 和TNP，包括在极端温度下、去甲肾上腺素、运动或限时进餐 挑战； ·使用EchoMRI和PixiMus DEXA进行身体成分分析，并研究 通过葡萄糖和胰岛素耐量试验、连续血糖监测、 和肝甘油三酯的产生； ·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 Core； ·协助调查人员为出版物产生高质量和可复制的研究结果， 拨款建议的试点数据，以及为人类临床试验提供信息的临床前研究结果； ·灵活并回应用户对新的和可定制的分析和程序的要求； ·参与活力计划，以量身定做的方式协助和培训新一代科学家 关注代表性不足的研究人员，增加生物医学研究的多样性 通过他们以前与MMPC的联系，参与MMH核心的调查人员已经 在能量代谢、生物能量学、身体成分、葡萄糖研究方面具有成熟的专业知识和能力 以及活体小鼠的脂类平衡、食物摄入量、代谢组学和肠道微生物区系。当与状态- 加州大学戴维斯分校最先进的设备、设施和核心分析实验室，MMH Core将是一种独特的、高度 对对新陈代谢生理学和心脏病理生理学感兴趣的国家研究人员具有影响力的科学资产 糖尿病和肥胖症。