PHYSIOLOGY OF MELANIN CONCENTRATING HORMONE IN OBESITY

肥胖中黑色素浓缩激素的生理学

• 批准号: 2900080
• 负责人: DAVID S LUDWIG
• 金额: $ 12.12万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-04-15 至 2000-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2900080
• 关键词: RNase protection assay; appetite regulatory center; bioenergetics; diet; embryonic stem cell; gene expression; gene targeting; genetically modified animals; hormone regulation /control mechanism; human genetic material tag; hypothalamic pituitary adrenal axis; immunocytochemistry; in situ hybridization; laboratory mouse; laboratory rat; leptin; melanins; neuropeptides; northern blottings; nucleic acid sequence; nutrition related tag; obesity; serotonin; single strand conformation polymorphism; southern blotting; stereotaxic techniques

DESCRIPTION (Taken from the applicant's abstract) The prevalence of obesity in the U.S. ranges from 25% overall to greater than 50% in some minority groups. Obesity may constitute the most common health problem in America, with associated morbidity and mortality rates equal to that of cancer. However, therapeutic options remain largely ineffectual. Thus, research into the pathophysiology and treatment of obesity assumes great significance to national health. Recent studies have demonstrated the importance of the brain, and specifically hypothalamus, to the regulation of body weight. Several hypothalamic substances have been identified which dramatically alter appetite and metabolic rate. In the present study, we have chosen to investigate the role of one particularly interesting hypothalamic neuropeptide, melanin concentrating hormone (MCH). Toward this end, transgenic mouse strains overexpressing the MCH gene will be produced. These strains should provide information regarding the physiologic actions of MCH in body weight regulation. In addition, the transgenic mice may constitute useful models for examining the actions of potential anti-obesity treatments. As an alternative approach, the effects of MCH administration by direct intracerebral injection will be studied. Dr. Ludwig's main research area is the neuroendocrine control of appetite and metabolism. In particular, he is interested in understanding how abnormal structure and function of the hypothalamus may underlie body weight disorders. The project will be conducted in the Division of Endocrinology and Metabolism of Beth Israel Hospital, Boston, under the supervision of Dr. Jeffrey Flier (Division Chief). Obesity and diabetes comprise the predominant research focus of the Division. Specific projects involve studies of insulin signal transduction, brown adipose tissue function, and leptin. The research environment contains state-of-the-art molecular biology, animal research, and transgenic facilities.

描述（摘自申请人的摘要） 美国的肥胖患病率总体为 25% 至更高 一些少数群体的比例超过 50%。 肥胖可能是最常见的 美国的健康问题及其相关的发病率和死亡率 与癌症同等。 然而，治疗选择在很大程度上仍然存在 无效的。 因此，对病理生理学和治疗的研究 肥胖对国民健康具有重要意义。 最近的研究证明了大脑的重要性， 特别是下丘脑，调节体重。 一些 已确定下丘脑物质可显着改变 食欲和新陈代谢率。 在本研究中，我们选择 研究一种特别有趣的下丘脑的作用 神经肽，黑色素浓缩激素（MCH）。 为了这个目的， 将产生过度表达 MCH 基因的转基因小鼠品系。 这些菌株应提供有关生理作用的信息 MCH 在体重调节中的作用。 此外，转基因小鼠可能 构成用于检查潜在抗肥胖作用的有用模型 治疗。 作为一种替代方法，MCH 管理的效果 将研究直接脑内注射。 路德维希博士的主要 研究领域是食欲和新陈代谢的神经内分泌控制。 在 特别是，他有兴趣了解异常结构和 下丘脑的功能可能是体重失调的原因。 这 项目将在内分泌和代谢科进行 波士顿贝斯以色列医院，在 Jeffrey Flier 博士的监督下 （科长）。 肥胖和糖尿病是主要研究对象 司的重点。 具体项目涉及胰岛素信号研究 转导、棕色脂肪组织功能和瘦素。 研究 环境包含最先进的分子生物学、动物研究、 和转基因设施。