The role of galanin-like peptide in energy balance and the involvement of inflammatory mediators: an in vivo physiological investigation

严重的体重增加（肥胖）或减少（恶病质，厌食症）带来了巨大的世界性医疗和社会问题。了解控制体重的事件将有助于开发治疗这些疾病的方法。体重的变化是由食欲和/或身体新陈代谢速率的改变引起的。这些过程是由大脑通过荷尔蒙和神经系统之间复杂的相互作用来控制的。然而，现在人们认为免疫系统也可能通过炎症分子（如细胞因子）的作用在调节体重方面发挥作用。瘦素是一种类似细胞因子的激素，由脂肪细胞产生，通过作用于大脑来调节体重。最近有研究表明，瘦素对啮齿动物食欲和体重的影响是由于细胞因子白介素-1 （IL-1）的变化。然而，瘦素调节IL-1产生的方式和所涉及的关键信使在很大程度上是未知的。甘丙肽样肽（GALP）是最近在大脑中发现的一种小分子。在啮齿类动物的大脑中注射GALP会导致食欲和体重下降，瘦素会像IL-1一样增加GALP的产生。我有初步结果表明GALP可能会影响啮齿动物IL-1的释放。本课题将测试GALP是否通过IL-1的产生影响食欲和体重。我的部分研究将使用没有IL-1的小鼠来观察它们是否对GALP有反应。我还将研究GALP在大脑中的作用，以及它如何刺激IL-1的释放。因此，这项工作将确定GALP是否通过产生炎症分子影响体重，并可能确定治疗体重调节障碍的新方法。

Severe weight gain (obesity) or loss (cachexia, anorexia) present massive world-wide medical and social problems. Understanding the events that control body weight will help to develop treatments for these conditions. Changes in body weight result from alterations in appetite and/or the rate of the body's metabolism. These processes are controlled by the brain through complex interactions between hormonal and nervous systems. However, it is now believed that the immune system may also play a role in the regulation of body weight through actions of inflammatory molecules such as cytokines. Leptin, a cytokine-like hormone is produced by fat cells and regulates body weight by acting in the brain. Recently it has been shown that the effects of leptin on appetite and body weight in rodents are due to changes in the cytokine interleukin-1 (IL-1). However, the way in which leptin regulates the production of IL-1 and the key messengers involved are largely unknown. Galanin-like peptide (GALP) is a small molecule that was identified recently in the brain. Injection of GALP into the brain of rodents causes a reduction in appetite and body weight, and leptin increases the production of GALP very much like IL-1. I have preliminary results to show that GALP may affect the release of IL-1 in rodents. This proposal will test whether GALP affects appetite and body weight through the production of IL-1. Part of my studies will use mice that do not have IL-1 to see if they can respond to GALP. I will also investigate where in the brain GALP is acting, and how it stimulates the release of IL-1. This work will, therefore, establish if GALP affects body weight by producing inflammatory molecules, and may also identify new ways of treating disorders of body weight regulation.