Investigating Ghrelin's Role in Regulating Energy Homeostasis

研究 Ghrelin 在调节能量稳态中的作用

• 批准号: 0417250
• 负责人: E. Gordon Grau
• 金额: --
• 依托单位: University of Hawaii
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-08-01 至 2007-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0417250&HistoricalAwards=false
• 关键词: Investigating; Ghrelin; Role; Regulating; Energy

Obesity is a major risk factor for many diseases, including, but not limited to, diabetes, cancer, arthritis, high blood pressure and cardiovascular disease. In the United States, roughly 300,000 deaths per year are associated with obesity and overweight. The recent discovery of ghrelin, a peptide found primarily in the stomach with potent stimulatory action on growth hormone release from the pituitary gland, has brought a new understanding of the regulation of energy balance. Ghrelin has been suggested to possess adipogenic, orexigenic and cardiovascular actions that might be independent from its GH stimulatory actions. The overall goal of the proposed research is to clarify the actions of ghrelin on growth and energy homeostasis in vertebrates including humans. Past work by the PIs have isolated ghrelin from the stomach of the tilapia, a euryhaline fish, with a potent GH-releasing activity as in mammals, and has provided preliminary evidence that ghrelin stimulates appetite and body weight gain in the tilapia, which appears to be a result of increased fat deposition. The PIs hypothesize that ghrelin will stimulate the production of fat independent from its GH stimulatory actions. In this proposal the mode of actions of ghrelin on energy homeostasis will be clarified, using CP-477335 (an orally active GH stimulatory compound) and a fish (tilapia) as a model. The specific aims of this proposal are: 1) To investigate whether ghrelin and CP-477335 alter fat deposition, specifically polyunsaturated fatty acids (PUFA), and production of growth factors and their binding proteins in the tilapia. 2) To characterize the actions of ghrelin and CP-477335 on fat deposition, PUFA metabolism and on growth factor production in the liver using culture of primary hepatocytes. The intellectual merit of the proposed studies in its novelty will provide invaluable groundwork for the understanding of ghrelin's actions in directing metabolic investment in vertebrates. To date, there are no reports on the effect of ghrelin on regulating PUFA metabolism in any vertebrate. The proposed studies will provide a comparative approach that will contribute greatly to the knowledge and understanding of how vertebrates partition available metabolic energy, which in turn could be used for the development of biotechnologies applicable to medicine and drugs/treatment associated with pathophysiological conditions.

肥胖是许多疾病的主要危险因素，包括但不限于糖尿病，癌症，关节炎，高血压和心血管疾病。 在美国，每年约有30万人死亡与肥胖和超重有关。 最近发现的生长素素是一种主要在胃中发现的肽，其对垂体释放生长激素释放的有效刺激作用使人们对能量平衡的调节有了新的了解。 已建议使用生长素素具有掺杂，骨髓和心血管作用，这些作用可能独立于其GH刺激作用。 拟议的研究的总体目标是阐明生长素对包括人类在内的脊椎动物的生长和能量稳态的行为。 PIS的过去工作已从罗非鱼的胃中分离出生长素蛋白，euryhaline鱼，具有有效的GH释放活性，如在哺乳动物中，并提供了初步证据，表明刺激性蛋白刺激了牛油蛋白的食欲和体重的增加，这似乎是脂肪沉积增加的结果。 PI假设生长素蛋白会刺激脂肪的产生，而不是其GH刺激作用。 在此提案中，将使用CP-477335（一种口服活跃的GH刺激化合物）和FISH（软骨）作为模型来阐明生长素素对能量稳态的作用方式。 该提案的具体目的是：1）研究生长素蛋白和CP-477335是否会改变脂肪沉积，特别是多不饱和脂肪酸（PUFA），以及生长因子的产生及其在牛lapia中的生长因子及其结合蛋白。 2）表征生长素蛋白和CP-477335对使用原发性肝细胞培养的脂肪沉积，PUFA代谢以及肝脏生长因子产生的作用。 拟议研究在新颖性中的智力优点将为理解何赫勒林在指导脊椎动物的代谢投资方面的行动提供宝贵的基础。 迄今为止，尚无关于生长素素对任何脊椎动物中PUFA代谢的影响的报道。 拟议的研究将提供一种比较方法，该方法将极大地有助于对脊椎动物分配的知识和理解，可用的代谢能量如何用于开发适用于医学和药物/与病理生理状况相关的药物/治疗的生物技术。