Neuroendocrine control of spontaneous physical activity

自发体力活动的神经内分泌控制

• 批准号: 6968129
• 负责人: MATTHIAS H TSCHOP
• 金额: $ 27.02万
• 依托单位: UNIVERSITY OF CINCINNATI
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-08-01 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6968129
• 关键词: body composition; body physical activity; genetically modified animals; ghrelin; hormone regulation /control mechanism; laboratory mouse; neuropeptides; nutrient intake activity

DESCRIPTION (provided by applicant): Obesity is one of the most urgent health problems, and all strategies for its prevention or treatment have failed. Increased sedentary behavior represents one reason for the increasing prevalence of obesity and its devastating consequences. Low physical activity levels are also a major determinant of body fat gain during overfeeding. We have recently generated preliminary data indicating that within the established regulatory system controlling food intake and body weight, the novel hormone ghrelin, as well at its main mediating target molecule in the brain AGRP, effectively suppress spontaneous physical activity (SPA) in rodent models. The putative regulation of spontaneous physical activity (SPA) by several other players in the same hormonal and neuronal networks, all of which are known to regulate food intake, has not previously been investigated in a systematic manner. We therefore propose to investigate a possible role for endogenous ghrelin and its immediate hypothalamic targets in the regulation of SPA. This series of studies might add a new and important element to the current model of energy balance regulation. Expanding the current model of food intake control to include a detailed characterization of the hormonal mechanisms regulating physical activity will promote our understanding of one of the major factors causing obesity. Equally important will be to develop a novel functional blueprint of a defined interactive network of pathways in the brain, which simultaneously regulates food intake, thermogenesis and SPA. This strategy may help to develop efficacious pharmacological agents to prevent and treat obesity in the future.

描述（由申请人提供）：肥胖是最紧迫的健康问题之一，所有预防或治疗肥胖的策略都失败了。久坐行为的增加是肥胖患病率不断上升及其破坏性后果的原因之一。体力活动水平低也是过度喂养期间体脂肪增加的主要决定因素。我们最近获得的初步数据表明，在控制食物摄入和体重的既定调节系统内，新型激素胃饥饿素及其大脑 AGRP 中的主要介导目标分子可有效抑制啮齿动物模型中的自发体力活动 (SPA)。同一激素和神经元网络中的其他几个参与者对自发体力活动（SPA）的假定调节，所有这些参与者都已知调节食物摄入量，但之前尚未以系统的方式进行研究。因此，我们建议研究内源性生长素释放肽及其直接下丘脑靶标在 SPA 调节中的可能作用。这一系列的研究可能会为当前的能量平衡调节模型添加一个新的重要元素。扩展当前的食物摄入控制模型，包括调节体力活动的激素机制的详细特征，将促进我们对导致肥胖的主要因素之一的理解。同样重要的是开发大脑中定义的交互通路网络的新颖功能蓝图，该网络同时调节食物摄入、产热和 SPA。这一策略可能有助于开发有效的药物来预防和治疗未来的肥胖症。