Neuroendocrine control of spontaneous physical activity

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症日益流行及其破坏性后果的原因之一。低体力活动水平也是过度喂养期间体脂增加的主要决定因素。我们最近产生的初步数据表明，在已建立的控制食物摄入量和体重的调节系统中，新型激素ghrelin及其在脑AGRP中的主要介导靶分子有效地抑制啮齿动物模型中的自发性身体活动（SPA）。在相同的激素和神经元网络中，其他几个参与者对自发性身体活动（SPA）的假定调节，所有这些都被认为是调节食物摄入的，以前没有被系统地研究过。因此，我们建议调查可能的作用，内源性ghrelin及其直接下丘脑的目标在SPA的调节。这一系列的研究可能会增加一个新的和重要的元素，目前的模式，能量平衡调节。扩大目前的食物摄入控制模型，包括一个详细的表征激素机制调节身体活动将促进我们的理解的主要因素之一，导致肥胖。同样重要的是开发一种新的功能蓝图，在大脑中定义一个相互作用的通路网络，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制剂，以预防和治疗肥胖的未来。

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.