GPR103 has multi-tissue effects on health and metabolism

我们正在经历代谢性疾病流行的流行，这些疾病主要与日益增加的肥胖症有关。随着身体变得肥胖，体内循环的脂肪(脂肪和胆固醇)和葡萄糖(糖)的数量会增加，这可能会导致动脉阻塞(增加心脏病发作或中风的几率)和糖尿病(增加肾衰竭或失明的几率)等疾病。治疗与肥胖相关的疾病近乎使NHS破产，因此，我们了解这些疾病的发展对于节省资金和促进健康生活至关重要。我们的新陈代谢是由不同的器官协调控制的。胰腺会产生胰岛素等激素来控制葡萄糖的吸收，而肝脏则可以根据需要吸收或产生更多的葡萄糖。同样，我们体内的脂肪实际上是以另一个器官的形式储存的：白色脂肪组织。腹部和大腿周围的白色脂肪组织不仅储存脂肪，还会产生荷尔蒙。然而，这些器官(胰腺、肝脏和脂肪组织)的协调最终是由大脑控制的。很少有因素以协调的方式作用于体内的所有这些器官。然而，最近，我们发现了一种名为QRFP的信使，它在大脑和其他器官中有增加食物摄入量、循环葡萄糖和脂肪产生的主要作用。我们将证明QRFP的不同类型的受体介导这些不同的作用。我们将培育不具有这两种受体的小鼠。然后，我们将生产一系列其他转基因小鼠，在这些小鼠中，我们可以只操纵体内产生QRFP的细胞。通过这种方式，我们将能够打开和关闭QRFP细胞，只需给小鼠一种药物。我们可以非常短暂地这样做，也可以在更长的时间内观察代谢紊乱的发展。相反，我们可以从没有QRFP的小鼠开始，然后一次将QRFP基因重新引入一个器官，以分离其不同的影响。最后，我们将能够使用小鼠来确定QRFP产生细胞如何与其他类型的细胞连接。这项工作将验证QRFP作为新陈代谢的关键调节因子。由于QRFP对不同的器官有不同的作用，因此开发针对其作用的药物可能是一个理想的靶点。一种可以阻断QRFP的药物将减少食物摄入量，使身体对胰岛素更敏感，从而更好地控制血糖，并减少脂肪组织产生的脂肪量。这样做会增加健康和幸福感。

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.