IMPC: Is Lrg1 an autocrine/paracrine regulator of thermogenesis in brown and beige adipose tissue? Implications for cardiometabolic disease.

背景：我们的身体将多余的能量以脂肪的形式储存在特殊的细胞中，称为白色脂肪细胞(形成白色脂肪组织)。但并不是所有的脂肪细胞都是一样的；棕色脂肪细胞(棕色脂肪组织)在寒冷中分解储存的脂肪产生热量，而米色脂肪细胞可以在两者之间切换，储存或燃烧脂肪。人们认为，棕色和米色脂肪细胞具有预防肥胖症和2型糖尿病的特性，因为它们的脂肪燃烧活动。然而，在衰老和肥胖期间，我们身体中棕色和米色脂肪的数量减少，而白色脂肪的数量增加。这可能会增加患代谢性疾病(如2型糖尿病)的风险。我们还不完全了解为什么在肥胖期间棕色和米色脂肪的数量会减少。我们的实验表明，脂肪细胞释放一种名为LRG1的蛋白质信号，这种信号可能会进入血液，降低棕色和米色脂肪细胞的脂肪燃烧能力。LRG1在2型糖尿病患者和肥胖者的血液中增加。血液中LRG1的浓度也随着年龄的增长而增加。我们还不确定LRG1是否会降低体内米色和棕色脂肪的脂肪燃烧能力，或者这是否会加速2型糖尿病的发展。研究目的：罗伯茨博士实验室的这项研究将确定“关闭”LRG1基因是否会增加米色和棕色脂肪细胞的数量，以及它们燃烧脂肪的能力。这项研究还将调查关闭LRG1基因是否可以预防肥胖和2型糖尿病。对社会和糖尿病患者的潜在好处：2型糖尿病是一个世界性的医疗挑战；据估计，全球有4.22亿人患有2型糖尿病。在英国，NHS每年花费140亿GB用于治疗糖尿病。了解肥胖是如何增加患这种疾病的风险的，可能会导致针对肥胖和2型糖尿病这两种全球流行病的新疗法。通过研究LRG1在调节米色和棕色脂肪细胞的脂肪燃烧能力中所起的作用，本研究希望确定LRG1是否是一个潜在的新的治疗靶点，以防止米色和棕色脂肪的丧失以及肥胖和2型糖尿病的发生。

Background: Our bodies store excess energy as fat inside special cells, called white fat cells (that form white adipose tissue). But not all fat cells are the same; brown fat cells (brown adipose tissue) break down stored fat to generate heat during exposure to cold, while beige fat cells can switch between the two, either storing or burning fat.It is thought that brown and beige fat cells have protective properties against obesity and type 2 diabetes, due to their fat burning activity. However, during aging and obesity the amount of brown and beige fat in our bodies decreases, while the amount of white fat increases. This may contribute to an increased risk of developing metabolic diseases such a type 2 diabetes. We do not yet fully understand why the amount of brown and beige fat decreases during obesity. Our experiments suggest that fat cells release a protein signal, known as Lrg1, which may enter the blood and decrease the fat burning ability of brown and beige fat cells. Lrg1 is increased in the blood of people with type 2 diabetes, and those who are obese. The concentration of Lrg1 in blood also increases with age. We don't yet know for certain whether Lrg1 decreases the fat burning ability of beige and brown fat in the body, or whether this contributes to accelerated development of type 2 diabetes. Research aims: This research in Dr Roberts' laboratory will determine whether "turning off" the gene for Lrg1 increases the amount of beige and brown fat cells, and their ability to burn fat. The research will also investigate whether switching off the Lrg1 gene protects against obesity and type 2 diabetes.Potential benefit to society and people with diabetes: Type 2 diabetes is a worldwide healthcare challenge; with an estimated 422 million people thought to have type 2 diabetes globally. In the UK the NHS spends £14 billion a year to treat diabetes. Understanding how obesity increases the risk of developing this disease, may lead to new treatments to target the twin global epidemics of obesity and type 2 diabetes. By studying the role Lrg1 plays in regulating the fat burning capacity of beige and brown fat cells, this research hopes to identify whether Lrg1 is a potential new therapy target to protect against the loss of beige and brown fat and the onset of obesity and type 2 diabetes.