Small Animal Metabolic Surgery (SAMS) Resource Core

小动物代谢外科 (SAMS) 资源核心

基本信息

批准号：
7943063
负责人：
LEE MICHAEL KAPLAN
金额：
$ 234.75万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-09-30 至 2012-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7943063
关键词：
Affect Animal Disease Models Animal Model Animals Behavior Behavior assessment Behavioral Blood Body Composition Body Temperature Body Weight Body Weight decreased Characteristics Cognitive Collaborations Communities Consult Control Animal DNA Data Databases Development Device Designs Devices Discipline Disease Eating Economics Educational workshop Evaluation Fluorescence Food Food Preferences Functional Imaging Genetic Glucose Goals Hand Human Image Individual Inflammatory Intervention Laboratories Liquid substance Magnetic Resonance Imaging Measurement Metabolic Metabolic Diseases Modeling Molecular Mus Nutritional Obesity Operative Surgical Procedures PET/CT scan Pattern Perioperative Care Phenotype Physical activity Physiologic pulse Physiological Physiology Preparation Preventive Procedures Proteomics Publishing RNA Rattus Regulation Regulatory Pathway Research Research Personnel Resources Rodent Rodent Model Series Services Specimen Surgical Models Taste Perception Techniques Therapeutic Tissues Training Work bariatric surgery burden of illness cost design drinking effective therapy experience feeding gastrointestinal genetic manipulation imaging modality implantable device in vivo insulin tolerance interest intraperitoneal investigator training metabolomics miniaturize mouse model neoplastic novel operation prevent programs public health relevance relating to nervous system repository respiratory response tool

项目摘要

DESCRIPTION (provided by applicant): The burden of disease attributable to obesity is enormous. Obesity is highly prevalent and associated with more than 60 metabolic, inflammatory, degenerative, cognitive, and neoplastic disorders. Broadly effective preventive and therapeutic strategies have been elusive, and rates of obesity continue to increase in all parts of the world. Among the current therapies for obesity, various forms of gastrointestinal weight loss surgery (GIWLS; bariatric surgery) have proven to be far and away the most effective and durable. Recent studies have demonstrated that these operations work primarily by affecting the physiological regulation of body weight. They affect multiple aspects of metabolic function, in some cases through mechanisms independent of weight loss or diminished food intake. These characteristics make use of GIWLS an attractive approach to examining physiological regulation of metabolic function. Using surgery to probe physiological mechanism is complementary to other means of studying these regulatory pathways, such as pharmacological or genetic manipulation. Combining the power of surgical, genetic, nutritional and pharmacological approaches will facilitate greater understanding of the cellular and molecular mechanisms underlying metabolic physiology in normal and disease states. The recent development of rat and mouse models of nearly all of the currently available GIWLS procedures will strongly facilitate this effort, but the technical difficulty and high cost of developing and maintaining these models is a formidable barrier to their use. The overall goal of this proposal is to establish a Small Animal Metabolic Surgery (SAMS) Core Resource whose services would reduce these barriers and facilitate use of these powerful models more broadly within the scientific community. More than 25 distinct rat and mouse surgical models of GIWLS procedures and related operations are available within the SAMS Core laboratory. The SAMS Core Resource will facilitate their effective use by (1) preparing and distributing surgical models and specimens from these models, (2) training investigators in their preparation and use, (3) performing metabolic and behavioral assessment of surgically manipulated animals, (4) assessing their physiology by in vivo functional imaging, and (5) establishing and maintaining a database of the effects of GIWLS in various rodent strains, genetically manipulated animals and disease models. The greater use of rodent models of GIWLS facilitated by the proposed SAMS Core will increase our understanding of the cellular and molecular regulation of metabolic function. It will also help to identify the mechanisms underlying the therapeutic benefits of these operations. Greater understanding of these mechanisms will contribute to the identification of new, more effective therapies for the several dozen diseases caused or promoted by obesity and will facilitate the development of more effective means of preventing and treating obesity itself. PUBLIC HEALTH RELEVANCE: The profound physiological effects of gastrointestinal weight loss surgery on body weight and metabolic function make these interventions valuable tools for probing the regulation of these physiological functions. The recent development of stable, reliable and reproducible models of these surgical procedures and related implantable devices in rats and mice strongly enhances their value to the scientific community, but the technical and economic barriers to their use are formidable. This proposal aims to establish a Small Animal Metabolic Surgery (SAMS) Core Resource Facility to facilitate the effective use of these rodent models by investigators working in the many disciplines affected by obesity and metabolic disorders. In response to the needs of Core users, the SAMS Core will prepare animal models for study by Core users, train investigators to prepare their models within their own laboratories, and use metabolic and behavioral assessment and several functional imaging modalities in vivo to characterize the effects of surgery in a variety of native, genetically modified or disease-bearing rodent models.

描述（由申请人提供）：可归因于肥胖的疾病负担是巨大的。肥胖症高度流行，并且与60多种代谢，炎症，退化，认知和肿瘤性疾病有关。广泛有效的预防和治疗策略是难以捉摸的，世界各地的肥胖率都在不断提高。在目前的肥胖疗法中，事实证明，各种形式的胃肠道减肥手术（GIWL；减肥手术）已被证明是最有效，最耐用的。最近的研究表明，这些操作主要是通过影响体重的生理调节而起作用。它们通过独立于体重减轻或食物摄入减少的机制来影响代谢功能的多个方面。这些特征使使用GIWLS是检查代谢功能的生理调节的有吸引力的方法。使用手术探测生理机制是研究这些调节途径的其他手段，例如药理或遗传操作。结合手术，遗传，营养和药理学方法的力量将有助于对正常和疾病状态中代谢生理的细胞和分子机制有更多了解。最近几乎所有当前可用的GIWLS程序的老鼠和鼠标模型的开发将极大地促进这项工作，但是开发和维护这些模型的技术困难和高成本是其使用的巨大障碍。该提案的总体目标是建立一个小型动物代谢手术（SAMS）核心资源，其服务将减少这些障碍并促进科学界更广泛地使用这些强大的模型。 SAMS核心实验室内有25多种超过25个不同的大鼠手术模型和相关操作。 The SAMS Core Resource will facilitate their effective use by (1) preparing and distributing surgical models and specimens from these models, (2) training investigators in their preparation and use, (3) performing metabolic and behavioral assessment of surgically manipulated animals, (4) assessing their physiology by in vivo functional imaging, and (5) establishing and maintaining a database of the effects of GIWLS in various rodent strains,遗传操纵的动物和疾病模型。提出的SAMS核心促进的GIWLS的啮齿动物模型的更大使用将增加我们对代谢功能的细胞和分子调节的理解。它还将有助于确定这些操作的治疗益处的基础机制。对这些机制的更多了解将有助于确定肥胖引起或促进的几十种疾病的新的，更有效的疗法，并有助于开发更有效的方法来预防和治疗肥胖本身。公共卫生相关性：胃肠道减肥手术对体重和代谢功能的深刻生理影响使这些干预措施有价值的工具可用于调节这些生理功能。这些外科手术程序以及大鼠和小鼠中相关植入器设备的稳定，可靠和可重复的模型的最新发展强烈增强了对科学界的价值，但是使用的技术和经济障碍是可强大的。该提案旨在建立一个小型动物代谢手术（SAM）核心资源设施，以促进在许多受肥胖和代谢性疾病影响的学科中工作的研究人员的有效使用这些啮齿动物模型。为了响应核心用户的需求，SAMS Core将准备核心用户的动物模型，培训研究人员在自己的实验室内准备模型，并使用代谢和行为评估以及体内的几种功能成像方式来表征各种本地人，遗传性疾病或疾病的啮齿动物模型中手术的影响。