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。超重的主要原因是摄入了比身体所需更多的食物，卡路里随后储存在脂肪中。这一点之所以重要，是因为不良的饮食和过多的体脂通常会对健康产生有害影响。这项应用的重点是澄清食物选择(为什么我们更喜欢蛋糕而不是卷心菜？)、膳食大小和体内脂肪积累背后的生物学因素。大脑代表着食欲的主协调者，利用离散的相互交织的回路不断地评估和回应能量供应的变化。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荷尔蒙。因此，清楚地了解NPY调节我们摄入的食物数量和我们选择的食物类型的确切机制是非常有意义的。然而，由于缺乏精确的工具，在这个方向上的发现一直受到阻碍。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的决定，以及这些卡路里是被使用还是储存在体内脂肪中。我们认为，大脑中称为孤束核的区域内的NPY执行这一基本功能。我们相信，该地区的NPY会做两件事来确保我们摄入足够的卡路里。其一，它增加了饥饿感、食物摄入量和对高卡路里食物的偏好。第二，它告诉身体将卡路里储存在脂肪中，这样我们以后需要的时候就会有能量供应。到目前为止产生的数据支持这一想法。在拟议的研究计划中，我们将结合最先进的技术，测试这种特殊来源的神经肽Y在饥饿和体脂中的作用。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法。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提供对食欲、食物选择、体重和体脂的生物学基础的基本见解，以及与预防和治疗肥胖症相关的发现。

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.