Defining the underpinnings of Neuropeptide Y (NPY)'s control of hunger and body fat

英国超过60%的人超重或肥胖。超重的主要原因是消耗的食物超过了身体的需要，然后将卡路里储存在脂肪中。这一点很重要的原因是因为不良的饮食和过量的身体脂肪通常对健康有不利影响。这项应用的重点是澄清食物选择背后的生物学（为什么我们更喜欢蛋糕而不是卷心菜？），膳食量和身体脂肪积累。大脑是食欲的主要协调者，它使用离散的交织回路来不断评估和响应能量可用性的变化。这个网络中的一个主要节点是一种名为脑神经肽Y（Npy）的大脑化学物质，它是一种强大的饥饿激素。因此，对Npy调节我们吃多少食物和我们选择的食物类型的精确机制的清晰理解是非常有趣的。然而，由于缺乏精确的工具，这方面的发现受到了阻碍。最近的技术进步现在提供了一种克服这一障碍的方法，提供了一种方法来发现大脑Npy的关键来源的位置，这些来源影响我们选择吃什么食物以及这些卡路里是否被使用或储存在身体脂肪中的决定。我们认为，在一个被称为孤束核的大脑区域内，Npy执行这一基本功能。我们相信这个区域的Npy做了两件事来确保我们有足够的卡路里。第一，它增加了饥饿感，食物摄入量和对高热量食物的偏好。第二，它告诉身体将卡路里储存在脂肪中，这样我们在需要的时候就有能量供应，目前的数据支持这一观点。使用最先进的技术组合，我们将在拟议的研究计划中测试这种特殊的Npy来源在饥饿和身体脂肪中的功能。这项工作很重要，因为我们相信我们已经找到了大脑控制饥饿和食物选择的基本方式。此外，我们认为我们已经发现了一种新的方式，大脑直接与身体脂肪对话，告诉它储存或消耗卡路里。我们预计，这些研究将为食欲、食物选择、体重和体脂的生物学基础提供基本的见解，这些发现与肥胖的预防和治疗有关。

More than 60% of people in the UK are overweight or obese. The primary cause of excess body weight is the consumption of more food than the body requires, calories that are then stored in fat. The reason this is important is because poor diet and excess body fat commonly has a detrimental impact on health. The focus of this application is clarifying the biology behind food choice (why do we prefer cake to cabbage?), meal size and body fat accumulation. The brain represents the master coordinator of appetite, employing discrete interwoven circuits to continually appraise and respond to changes in energy availability. A principal node within this network is a brain chemical called brain Neuropeptide Y (Npy), which is a powerful hunger hormone. Therefore, a clear understanding of the precise mechanism through which Npy modulates how much food we eat and the types of food we choose is of intense interest. However, discoveries in this direction have been hindered by a lack of precise tools. Recent technological advances now provide a means to overcome this obstacle, affording a way to discover the location of crucial sources of the brain's Npy that influence our decisions about what foods we choose to eat and whether these calories are used or stored in body fat. We think that Npy within a brain region called the nucleus of the solitary tract performs this essential function. We believe Npy in this region does two things to make sure that we have enough calories on board. One, it increases hunger, food intake and a preference for high calorie foods. And two, it tells the body to store calories in fat so that we have a supply of energy later if we need it. Data generated thus far support this idea. Using a combination of state of the art techniques, we will test the function of this special source of Npy in hunger and body fat in the proposed research programme. This work is important because we believe we have found an essential way that the brain controls hunger and food choice. Moreover, we think we have uncovered a new way that the brain talks directly to body fat, telling it to either store or expend calories. We anticipate that these studies will provide fundamental insight into the biological underpinnings of appetite, food choice, body weight and body fat, findings relevant to the prevention and treatment of obesity.