Small Animal Metabolic Surgery (SAMS) Resource Core

小动物代谢外科 (SAMS) 资源核心

• 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
• 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

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）：由肥胖引起的疾病负担是巨大的。肥胖症非常普遍，与60多种代谢、炎症、退行性、认知和肿瘤疾病相关。广泛有效的预防和治疗战略一直难以实现，世界各地的肥胖率继续上升。在目前的肥胖症治疗中，各种形式的胃肠道减肥手术（GIWLS;减肥手术）已被证明是最有效和最持久的。最近的研究表明，这些手术主要通过影响体重的生理调节来起作用。它们影响代谢功能的多个方面，在某些情况下，通过独立于体重减轻或食物摄入减少的机制。这些特点使GIWLS成为一种有吸引力的方法来检查代谢功能的生理调节。使用手术来探测生理机制是对研究这些调节途径的其他手段的补充，例如药理学或遗传操作。结合手术、遗传、营养和药理学方法的力量，将有助于更好地理解正常和疾病状态下代谢生理学的细胞和分子机制。最近开发的大鼠和小鼠模型，几乎所有目前可用的GIWLS程序将大大促进这一努力，但技术上的困难和高成本的开发和维护这些模型是一个可怕的障碍，他们的使用。该提案的总体目标是建立一个小动物代谢外科（SAMS）核心资源，其服务将减少这些障碍，并促进在科学界更广泛地使用这些强大的模型。在SAMS核心实验室内，有超过25种不同的大鼠和小鼠GIWLS手术模型和相关手术。SAMS核心资源将通过以下方式促进其有效使用：（1）准备和分发手术模型和这些模型的标本，（2）培训研究人员准备和使用这些模型，（3）对手术操作的动物进行代谢和行为评估，（4）通过体内功能成像评估其生理学，以及（5）建立和维护GIWLS在各种啮齿动物品系、基因操作动物和疾病模型中的作用的数据库。更多地使用啮齿类动物模型的GIWLS促进拟议的SAMS核心将增加我们的细胞和分子调节代谢功能的理解。这也将有助于确定这些手术的治疗益处的机制。对这些机制的更深入了解将有助于确定新的、更有效的治疗肥胖引起或促进的几十种疾病的方法，并将促进开发更有效的预防和治疗肥胖本身的方法。 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成为探索这些生理功能调节的有价值的工具。最近在大鼠和小鼠中开发的这些外科手术和相关植入式装置的稳定、可靠和可重复模型大大提高了它们对科学界的价值，但它们的使用面临着巨大的技术和经济障碍。该提案旨在建立一个小动物代谢外科（SAMS）核心资源设施，以促进在受肥胖和代谢紊乱影响的许多学科中工作的研究人员有效利用这些啮齿动物模型。为了满足核心用户的需求，SAMS核心将为核心用户的研究准备动物模型，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几种体内功能成像模式来表征各种原生，转基因或携带疾病的啮齿动物模型中的手术效果。