Dissecting thermogenesis by brown adipose tissue and skeletal muscle in lean and obese subjects

超重或肥胖的人数继续增加，肥胖会增加你患其他许多疾病的风险，如2型糖尿病、高血压、心脏病、某些癌症，并减少预期寿命。肥胖还与死于新冠肺炎的更高风险有关。因此，迫切需要新的肥胖症治疗方法来改善健康。减肥可以通过减少我们摄入的能量或增加我们燃烧的能量来实现。当人们体重增加时，你体内的脂肪量就会增加，这也被称为“白色脂肪”，这种脂肪主要是用来储存多余的能量的。然而，在你的身体里还有另一种脂肪叫做棕色脂肪，这是一种非常特殊的脂肪，因为它的主要作用是在寒冷的环境中燃烧能量来保暖。有趣的是，肥胖的人比正常体重的人拥有更少的棕色脂肪，重要的是，确实有棕色脂肪的肥胖者比没有棕色脂肪的肥胖者更不容易患糖尿病和心脏病。我们体内的棕色脂肪的数量也可以增加，因此，人们对如何激活棕色脂肪作为一种新的治疗方法很感兴趣，以帮助降低患糖尿病或心脏病的几率。然而，我们对棕色脂肪如何产生热量的理解还不是很清楚，部分原因是很难测量它在人体中的活动，而且依赖于特殊类型的扫描。也不清楚肥胖者的棕色脂肪是否与瘦人的棕色脂肪相比功能不正常。在这项研究中，我们将测量棕色脂肪在瘦人和肥胖者中的作用，当他们被置于温暖和寒冷的环境中时。我们将在瘦和肥胖成年人的棕色脂肪、白色脂肪和肌肉组织中放置特殊的管子，以测量这些组织在产生热量时使用了多少糖、脂肪和其他物质。这将使我们能够更完整地了解棕色脂肪是如何利用这些物质产生热量的。我们之前已经证明，人类的棕色脂肪会产生一种名为乳酸的物质，我们还将研究乳酸对棕色脂肪功能的重要性，以及棕色脂肪如何利用这种乳酸产生热量。最后，我们知道棕色脂肪可以与身体其他重要组织沟通以改善健康，我们将通过测量棕色脂肪在瘦小和肥胖的成年人身上产生哪些物质来研究棕色脂肪是如何做到这一点的。这项研究将揭示棕色脂肪如何对健康产生有益影响，并确定肥胖如何改变棕色脂肪的功能。这很可能确定新的靶点，使我们能够开发新的治疗方法，使棕色脂肪发挥更好的作用。最终，这可能会带来更好的治疗方法，帮助人们减肥、治疗糖尿病和预防心脏病。

The number of people who are either overweight or obese continues to increase, and being obese increases your risk of developing many other diseases such as type 2 diabetes, high blood pressure, heart disease, certain cancers and reduces life expectancy. Obesity is also associated with a higher risk of dying from covid-19. As such, new treatments for obesity are urgently required to improve health. Weight loss can be achieved either by reducing how much energy we eat or by increasing the amount of energy we burn. When people gain weight the amount of fat in your body increases, this is also called 'white fat' and this type of fat is there mainly to store excess energy. However, there is another type of fat in your body called brown fat, this is a very special type of fat in that its main role is to burn energy to keep us warm when we're in a cold environment. Interestingly, people who are obese have less brown fat than people of normal weight, importantly though obese people who do have brown fat are less likely to develop diabetes and heart disease than obese people without brown fat. The amount of brown fat we have in our body can also be increased, as such there is much interest in working out how to activate brown fat as a new treatment to help reduce the chances of developing diabetes or heart disease. However, our understanding of how brown fat generates heat is not well understood, in part this is because it is difficult to measure its activity in humans and relies on special types of scans. It is also unclear whether the brown fat in obese individuals doesn't function properly compared to the brown fat in lean people. In this research we will measure how brown fat works in lean and obese people when they are placed in the warm and the cold. We will place special tubes in the brown fat, white fat and muscle tissue of lean and obese adults to measure how much sugar, fat and other substances these tissues use when generating heat. This will allow us to build a more complete picture of how brown fat uses these substances to produce heat. We have previously shown that brown fat in humans produces a lot of a substance called lactate, we will also work out the importance of lactate to brown fat function and how brown fat uses this lactate to generate heat. Finally, we know that brown fat can communicate with other important tissues in the body to improve health, we will investigate how brown fat does this by measuring which substances brown fat produces in lean and obese adults. This research will reveal how brown fat produces its beneficial effects on health and identify how obesity changes brown fat function. This may well identify new targets which will allow us to develop new treatments to make brown fat work better. This may in time lead to better therapies to help people lose weight, treat diabetes and prevent heart disease.