Lipid to store? Send in the Seipin: Dissecting the Critical Roles for Seipin in Cellular and Organismal Lipid Storage.

储存脂肪是在能量过剩时保持能量的一种非常有效的方法，这样当营养物质不那么容易获得时，它就可以被使用。从化学上讲，脂肪以包裹着特殊蛋白质的液滴的形式储存在活细胞内。这在酵母菌等仅由一个细胞组成的简单生物体以及人类中都是如此。在人类和其他动物中，大多数脂质储存在专门的脂肪细胞中。动物进化出脂肪细胞，这样储存的脂肪就能与体内的其他细胞隔离开来。这很重要，因为过多的脂肪会对其他细胞有毒。例如，在肥胖中，脂肪细胞被淹没，脂肪溢出，在肝脏和血管壁等地方堆积。这会导致肥胖相关的疾病，如脂肪肝、糖尿病和心脏病。我们感兴趣的是一种叫做seipin的蛋白质，它在体内脂肪的储存中起着关键作用。少数缺乏这种蛋白质的人不能产生脂肪细胞。因为这些人没有地方可以安全地储存脂肪，他们会患上脂肪肝、严重的糖尿病和心血管疾病。seipin蛋白的确切作用尚不清楚，但它是干细胞转化为新的脂肪细胞所必需的。Seipin还参与使脂肪滴在细胞内正确形成。近年来，我们发现seipin就像细胞中的一个停靠站，组织其他蛋白质，使它们能够协同工作并发挥重要功能。通过这样做，seipin组织蛋白质来调节细胞中的脂肪储存，同时也组织蛋白质一起将干细胞转化为新的脂肪细胞。我们知道一些与seipin结合的蛋白质，但我们不知道哪些是脂肪细胞发育或细胞内脂肪储存所需要的。该项目将专门针对不同的蛋白质结合事件，以确定seipin中心以及哪些相关蛋白质是如何控制脂肪储存和新脂肪细胞生成的。总的来说，这个项目将确切地找出为什么我们需要seipin来制造新的脂肪细胞，但也将揭示关于细胞如何制造和储存脂肪的新信息。这些信息可以用来寻找新的方法来改善人类的脂肪储存，这是随着我们年龄的增长或体重的增加而出现的问题。如果我们能找到让脂肪细胞正常工作的方法，就能找到预防或治疗与肥胖和衰老有关的主要疾病的新方法，比如糖尿病、心脏病和几种癌症。

Storing fat is a highly effective way to retain energy in times of excess so that it can be used later when nutrients are less freely available. Chemically, fat is stored inside living cells in droplets coated in specialised proteins. This is true in simple organisms such as yeast, which are made up of only one cell, as well as in humans. In humans and other animals, most lipid is stored in specialised fat cells. Animals evolved fat cells so that the stored fat could be kept away from other cells in the body. This is important because too much fat can be toxic to these other cells. For example, in obesity fat cells get overwhelmed and the fat overflows, building up in places like the liver and walls of the blood vessels. This causes obesity associated diseases like fatty liver, diabetes and heart disease. We are interested in a protein called seipin which plays a critical role in the storage of fat in the body. A rare group of people who lack the seipin protein are not able to make fat cells. Because these people have nowhere to safely store fat they get fatty liver disease, severe diabetes and cardiovascular problems. Exactly what the seipin protein does remains unclear but it is needed to allow stem cells to turn into new fat cells. Seipin is also involved in making fat droplets form properly inside the cells. In recent years we have discovered that seipin works like a docking station in the cells organising other proteins so that they can work together and perform important functions. By doing this seipin organises proteins to regulate fat storage in the cell but also organises proteins that work together to turn stem cells into new fat cells. We know some of the proteins that seipin binds, but we don't know which ones are actually needed for fat cell development or the storage of fat within the cells.This project will specifically target different protein binding events to work out exactly how the seipin hub, and which associated proteins, control fat storage and new fat cell generation.Overall, this project will work out exactly why we need seipin to make new fat cells but will also reveal new information about how cells make and store fat. This information can then be used to find new ways to improve fat storage in humans, something that goes wrong as we age or gain weight. If we find ways to can make fat cells work properly this could reveal new ways to prevent or treat major diseases linked to obesity and ageing like diabetes, heart disease and several forms of cancer.