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）：肥胖是最紧急的健康问题之一，其预防或治疗的所有策略都失败了。久坐行为的增加代表了肥胖症患病率增加及其毁灭性后果的原因之一。低体育锻炼水平也是过度喂养过程中体内脂肪增加的主要决定因素。我们最近生成了初步数据，表明在既定的调节系统中，控制食物摄入和体重，新型激素生长素蛋白，以及其在脑AGRP中的主要介导靶分子中，有效地抑制了啮齿动物模型中的自发体育活动（SPA）。以前尚未以系统的方式研究同一激素和神经元网络中其他几名参与者对自发体育锻炼（SPA）的推定调节（SPA）。因此，我们建议研究内源性生长素素及其直接下丘脑在水疗中的可能作用。这一系列研究可能会为当前的能量平衡调节模型增加一个新的重要因素。扩展当前的食物摄入控制模型，包括调节体育活动的激素机制的详细表征，将促进我们对导致肥胖症的主要因素之一的理解。同样重要的是，要开发出大脑中定义的互动途径网络的新型功能蓝图，该途径同时调节食物摄入量，热生成和水疗中心。该策略可能有助于开发有效的药理学剂，以预防和治疗肥胖症。