Small Animal Metabolic Surgery (SAMS) Resource Core

描述（由申请人提供）：肥胖导致的疾病负担是巨大的。肥胖非常普遍，与60多种代谢、炎症、退行性、认知和肿瘤疾病有关。广泛有效的预防和治疗策略一直难以捉摸，世界各地的肥胖率继续上升。在目前的治疗肥胖的方法中，各种形式的胃肠道减肥手术（gils；减肥手术）已被证明是最有效和持久的。最近的研究表明，这些手术主要是通过影响体重的生理调节来起作用的。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减少食物摄入的机制。这些特点使得利用gils是一种有吸引力的方法来检查代谢功能的生理调节。利用外科手术来探索生理机制是对其他研究这些调控途径的补充，如药理学或基因操作。结合外科、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。目前几乎所有可用的gils方法的大鼠和小鼠模型的最新发展将有力地促进这一努力，但开发和维护这些模型的技术难度和高成本是其使用的巨大障碍。本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，并促进这些强大模型在科学界更广泛的使用。SAMS核心实验室提供超过25种不同的大鼠和小鼠gwl手术模型和相关手术。SAMS核心资源将通过(1)准备和分发来自这些模型的手术模型和标本，(2)培训研究人员准备和使用这些模型，(3)对手术操纵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，以及(5)建立和维护一个关于giwl在各种啮齿动物品系、基因操纵动物和疾病模型中的影响的数据库。SAMS Core促进了对giwl啮齿动物模型的更多使用，将增加我们对代谢功能的细胞和分子调控的理解。它也将有助于确定这些手术治疗效益的潜在机制。对这些机制的进一步了解将有助于确定新的、更有效的治疗方法，以治疗由肥胖引起或促进的几十种疾病，并将促进开发更有效的预防和治疗肥胖本身的方法。

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.