GPR103 has multi-tissue effects on health and metabolism

GPR103 对健康和新陈代谢具有多组织影响

基本信息

批准号：
BB/J005509/1
负责人：
Simon Luckman
金额：
$ 53.74万
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：
2012
资助国家：
英国
起止时间：
2012 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=BB%2FJ005509%2F1
关键词：
GPR103 multi tissue effects health

项目摘要

We are experiencing an epidemic in the prevalence of metabolic diseases which are associated mainly with increasing obesity. As the body becomes obese there is an increase in the amount of lipid (fat and cholesterol) and glucose (sugar) circulating in the body, which can lead to diseases such as blocked arteries (increasing the chances of heart attacks or stroke) and diabetes (increasing the chances of kidney failure or blindness). Treating the diseases associated with obesity is close to bankrupting the NHS and, therefore, it is critical that we understand the development of these diseases to save money and promote healthy living. Our metabolism is controlled by different organs in a coordinated fashion. The pancreas produces hormones like insulin to control glucose uptake, while the liver can take up or produce more glucose depending on needs. Likewise, the fat in our bodies is actually stored as another organ: white adipose tissue. White adipose tissue around our abdomens and thighs, not only stores fat, but it too produces hormones. The coordination of these organs (pancreas, liver and adipose tissue), however, is ultimately governed by the brain. Few factors act in a coordinated manner on all of these organs in the body. However, recently, we have found a messenger, called QRFP, has major actions in the brain and other organs to increase food intake, circulating glucose and fat production. We will demonstrate that different types of receptors for QRFP mediate these different actions. We will produce mice which do not have the two types of receptor. Then we will produce a series of other genetically-modified mice in which we can manipulate just the cells in the body that produce QRFP. In this way, we will be able to switch the QRFP cells on and off, simply by giving the mice a drug. We can do this very briefly, or over a longer period to see the development of metabolic disorders. Instead, we can start with a mouse that has no QRFP and then genetically re-introduce QRFP into one organ at a time, to isolate its different effects. Finally, we will be able to use the mice to determine how QRFP-producing cells connect with other cell types. This work will validate QRFP as a key regulator of metabolism. As QRFP has many different effects on different organs, it may be an ideal target to develop drugs against its actions. A drug that can block QRFP would reduce food intake, make the body more sensitive to insulin so that glucose is controlled better, and reduce the amount of fat produced by adipose tissue. Doing this would lead to increasing health and wellbeing.

我们在代谢疾病的患病率中经历了主要与肥胖症增加有关的流行病。随着身体肥胖，体内循环的脂质（脂肪和胆固醇）和葡萄糖（糖）的量增加，这可能导致疾病，例如阻塞动脉（增加心脏病或中风的机会）和糖尿病（增加肾衰竭或失明的机会）。治疗与肥胖相关的疾病几乎几乎破产了NHS，因此，至关重要的是，我们必须了解这些疾病的发展以节省金钱并促进健康的生活。我们的新陈代谢由不同的器官以协调的方式控制。胰腺产生诸如胰岛素之类的激素以控制葡萄糖摄取，而肝脏可以根据需求占用或产生更多的葡萄糖。同样，我们体内的脂肪实际上被存储为另一个器官：白色脂肪组织。我们的腹部和大腿周围的白色脂肪组织不仅储存脂肪，而且也会产生激素。然而，这些器官（胰腺，肝脏和脂肪组织）的协调最终由大脑控制。很少有因素以协调的方式对体内所有这些器官作用。但是，最近，我们发现一个名为QRFP的使者在大脑和其他器官中采取了重大作用，以增加食物摄入量，循环葡萄糖和脂肪产生。我们将证明QRFP的不同类型的受体介导了这些不同的作用。我们将产生没有两种受体的小鼠。然后，我们将产生一系列其他遗传改性的小鼠，在其中我们只能操纵体内产生QRFP的细胞。这样，我们将能够通过给小鼠药物来打开和关闭QRFP细胞。我们可以非常短暂地做到这一点，也可以在更长的时间内看到代谢障碍的发展。取而代之的是，我们可以从没有QRFP的小鼠开始，然后一次将QRFP重新介绍为一个器官，以隔离其不同的效果。最后，我们将能够使用小鼠来确定产生QRFP的细胞如何与其他细胞类型连接。这项工作将验证QRFP作为代谢的关键调节剂。由于QRFP对不同的器官具有许多不同的影响，因此它可能是针对其作用开发药物的理想目标。可以阻止QRFP的药物会减少食物摄入量，使人体对胰岛素更敏感，从而更好地控制葡萄糖，并减少脂肪组织产生的脂肪量。这样做会导致健康和福祉的日益增加。

项目成果

期刊论文数量（3）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

The hypothalamic RFamide, QRFP, increases feeding and locomotor activity: The role of Gpr103 and orexin receptors.

DOI：
10.1371/journal.pone.0275604
发表时间：
2022
期刊：
PLOS ONE
影响因子：
3.7
作者：
Cook, Chris;Nunn, Nicolas;Worth, Amy A.;Bechtold, David A.;Suter, Todd;Gackeheimer, Susan;Foltz, Lisa;Emmerson, Paul J.;Statnick, Michael A.;Luckman, Simon M.
通讯作者：
Luckman, Simon M.

Physiological Roles of GPR10 and PrRP Signaling.