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

甘丙肽样肽在能量平衡中的作用和炎症介质的参与：体内生理学研究

• 批准号: BB/E007481/1
• 负责人: Catherine Lawrence
• 金额: $ 70.14万
• 依托单位: University of Manchester
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2007
• 资助国家: 英国
• 起止时间: 2007 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FE007481%2F1
• 关键词: role; galanin; like; peptide; energy

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.

严重的体重增加(肥胖)或减轻(恶病质、厌食症)造成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针对这些疾病的治疗方法。体重的变化是由食欲和/或身体新陈代谢速度的变化引起的。这些过程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。然而，现在人们认为，免疫系统也可能通过细胞因子等炎症分子的作用在调节体重方面发挥作用。瘦素是一种细胞因子样激素，由脂肪细胞产生，通过作用于大脑来调节体重。最近的研究表明，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产生的方式以及涉及的关键信使在很大程度上是未知的。甘丙素样肽(GALP)是最近在大脑中发现的一种小分子。将GALP注射到啮齿类动物的大脑中会导致食欲和体重下降，而瘦素与IL-1一样会增加GALP的产生。我有初步结果表明，GALP可能会影响啮齿动物体内IL-1的释放。这项提案将测试GALP是否通过产生IL-1影响食欲和体重。我的部分研究将使用没有IL-1的小鼠，看看它们是否对GALP有反应。我还将调查GALP在大脑的哪个部位起作用，以及它是如何刺激IL-1的释放的。因此，这项工作将确定GALP是否通过产生炎症分子来影响体重，并可能找到治疗体重调节障碍的新方法。

项目成果

Galanin-like peptide (GALP) is a hypothalamic regulator of energy homeostasis and reproduction.

• DOI: 10.1016/j.yfrne.2010.06.001
• 发表时间: 2011-01
• 期刊: FRONTIERS IN NEUROENDOCRINOLOGY
• 影响因子: 7.4
• 作者: Lawrence, Catherine;Fraley, Gregory S.
• 通讯作者: Fraley, Gregory S.

Interleukin-1 mediates the anorexic and febrile actions of galanin-like Peptide.

Interleukin-1 介导甘丙肽样肽的厌食和发热作用。

• DOI: 10.1210/en.2008-0252
• 发表时间: 2008
• 期刊: Endocrinology
• 影响因子: 4.8
• 作者: Man PS

The effects of galanin-like peptide on energy balance, body temperature and brain activity in the mouse and rat are independent of the GALR2/3 receptor.

• DOI: 10.1111/j.1365-2826.2007.01625.x
• 发表时间: 2008-01
• 期刊: Journal of neuroendocrinology
• 影响因子: 3.2
• 作者: Man PS;Lawrence CB
• 通讯作者: Lawrence CB

Galanin-like peptide: neural regulator of energy homeostasis and reproduction.

• DOI: 10.1007/978-3-0346-0228-0_18
• 发表时间: 2010
• 期刊: Experientia supplementum
• 作者: C. Lawrence;G. Fraley

Galanin-like peptide modulates energy balance by affecting inflammatory mediators?

甘丙肽样肽通过影响炎症介质来调节能量平衡？

• DOI: 10.1016/j.physbeh.2009.02.041
• 发表时间: 2009
• 期刊: Physiology & behavior
• 影响因子: 2.9
• 作者: Lawrence CB