Neuroendocrine control of spontaneous physical activity

描述(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量喂养期间身体脂肪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及其在大脑AGRP中的主要中介靶分子，有效地抑制了啮齿动物模型中的自发体力活动(SPA)。在相同的荷尔蒙和神经元网络中，其他几个参与者对自发身体活动(SPA)的假定调节都是已知的，这些都是调节食物摄入量的，以前还没有系统地研究过。因此，我们建议研究内源性Ghrelin及其直接下丘脑靶点在调节SPA中的可能作用。这一系列研究可能会为当前的能源平衡调控模式添加一个新的重要元素。扩展当前的食物摄入量控制模型，包括调节体力活动的荷尔蒙机制的详细特征，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，开发大脑中已定义的相互作用的通路网络的新功能蓝图，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理药物来预防和治疗肥胖症。

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.