Regulation of Food Intake and Body Weight by Hypothalamic ERAlpha

下丘脑 ERAlpha 对食物摄入量和体重的调节

• 批准号: 7148400
• 负责人: Deborah J Clegg
• 金额: $ 28.4万
• 依托单位: UNIVERSITY OF CINCINNATI
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-15 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7148400
• 关键词: appetite regulatory center; behavioral /social science research tag; bioenergetics; body weight; brain regulatory center; estrogen receptors; estrogens; hormone regulation /control mechanism; hormone sensitivity /resistance; hypothalamus; laboratory mouse; laboratory rat; leptin; nutrient intake activity; nutrition related tag; receptor expression; weight control

DESCRIPTION (provided by applicant): Obesity and its associated health disorders and costs are increasing. Fat distribution and the associated risk for developing cardiovascular problems, type-2 diabetes mellitus, certain cancers and other disorders differ for men and women. Men and post-menopausal women have greater risk of developing complications of obesity than younger women. The ventromedial hypothalamus (VMM) is an important regulator of energy homeostasis, and two of its sub-areas, the ventrolateral portion (VL VMM) and the arcuate (ARC) respond to hormones and other signals to control energy intake and expenditure. When large VMM lesions are made that include both the VL VMM and the ARC, animals, especially females, eat more food, burn less energy and become obese. Because both the ARC and the VMN contain dense estrogen receptors (specifically ERa), because reducing estrogen also causes obesity, and because estrogen mediates the sensitivity of the brain to leptin, we hypothesize that when VMM lesions are made, the reduction of estrogen signaling and consequent reduction in leptin signaling are what results in increased body weight. The aims of this proposal follow directly from these observations, and will determine the relative contribution of estrogen signaling through ERa in the regulation of food intake and body weight in the ARC and the VL VMN. Specifically, we will determine if estrogen signaling through ERa in the VL VMN or the ARC is necessary and/or sufficient to regulate food intake and body weight. Our findings will have direct relevance in increasing our understanding of the mechanisms by which estrogen regulates body weight, and this will assist in determining potential therapeutic agents for menopausal women to decrease adiposity and the propensity of diseases associated with obesity.

描述（由申请人提供）：肥胖及其相关的健康障碍和成本正在增加。脂肪分布以及出现心血管问题，2型糖尿病，某些癌症和其他疾病的风险不同。与年轻女性相比，男性和绝经后妇女患肥胖并发症的风险更大。腹侧下丘脑（VMM）是能量稳态的重要调节剂，其两个亚区域，腹外侧部分（VL VMM）和弧形（ARC）（ARC）对激素和其他信号响应，以控制能量的摄入和支出。当制造出大型VMM病变时，包括VL VMM和ARC时，动物，尤其是雌性，吃更多的食物，燃烧的能量更少并变得肥胖。因为ARC和VMN都包含致密的雌激素受体（特别是ERA），因为雌激素还会导致肥胖，并且雌激素会介导大脑对瘦素的敏感性，因此我们假设当产生VMM病变时，雌激素信号传导和脂蛋白信号减少的减少会增加体重的减少。该提案的目的直接来自这些观察结果，并将确定雌激素信号传导通过ERA在ARC和VL VMN中的食物摄入和体重调节中的相对贡献。具体而言，我们将确定在VL VMN中通过ERA的雌激素信号传导是否需要和/或足以调节食物摄入和体重。我们的发现将直接相关，以增加我们对雌激素调节体重的机制的理解，这将有助于确定绝经女性的潜在治疗剂，以减少肥胖和肥胖相关的疾病倾向。