Neuroendocrine control of spontaneous physical activity

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日益流行及其破坏性后果的一个原因。低体力活动水平也是过度进食期间体脂增加的主要决定因素。我们最近获得的初步数据表明，在已建立的控制食物摄入和体重的调节系统中，新型激素ghrelin及其主要介导靶分子大脑AGRP有效地抑制了啮齿动物模型的自发身体活动（SPA）。在相同的激素和神经网络中，其他几个参与者对自发身体活动（SPA）的假设调节，所有这些都被认为是调节食物摄入的，以前没有系统地研究过。因此，我们建议研究内源性胃饥饿素及其直接下丘脑靶点在SPA调节中的可能作用。这一系列的研究可能会为目前的能量平衡调节模型增加一个新的重要元素。扩大目前的食物摄入控制模型，包括对调节身体活动的激素机制的详细描述，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，开发一种新的功能蓝图，描述大脑中一个明确的互动通路网络，它同时调节食物摄入、产热和SPA。这一策略可能有助于在未来开发有效的药物来预防和治疗肥胖。

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.