Elucidating the Function of BSCL2, a Critical Regulator of Human Fat Development

鉴于肥胖率居高不下且不断上升，过量脂肪对健康的有害影响是众所周知的。然而，脂肪含量异常低(脂肪营养不良)的情况要罕见得多，因此受到的关注要少得多。事实上，身体脂肪过多或过少都与类似的疾病密切相关，如糖尿病和心脏病，这些疾病是痛苦和死亡的主要原因。这表明，对我们来说，开发适量的脂肪，并使其能够有效地储存和释放营养物质，并适当地分泌其产生的激素是很重要的。增加脂肪量需要从前体细胞产生新的脂肪细胞(脂肪细胞)，因此仔细控制这一过程对健康至关重要。这项工作主要是通过在实验室中可以转化为脂肪细胞的细胞和研究调节这一过程的基因来检查这一过程。具体地说，我们关注的是一种名为BSCL2的基因，我们知道它对人类脂肪组织的形成至关重要，因为它的中断会导致几乎完全缺乏脂肪。我们最近发现，这个基因调节脂肪细胞的形成过程，但它实现这一过程的确切机制尚不清楚。这项工作旨在确定BSCL2如何控制脂肪细胞的形成，确定与其相互作用的蛋白质，以及BSCL2本身是如何受到调控的。通过这种方式，我们将更多地了解脂肪细胞是如何发育的。这些信息不仅对于最终找到治疗这种非常特殊、罕见但具有破坏性的脂肪营养不良的方法至关重要，而且对于了解肥胖症的发展和治疗也非常相关。

Given the high and increasing rates of obesity, the harmful effects of excess fat on health are well known. However, conditions in which fat mass is abnormally low (lipodystrophies) are much rarer and so receive far less attention. In fact, having either too much or too little body fat are each strongly associated with similar diseases such as diabetes and heart disease which are major causes of suffering and mortality. This shows that it is important for us to develop just the right amount of fat and for it to be able to work efficiently to store and release nutrients and secrete the hormones it produces appropriately. Increasing fat mass involves making new fat cells (adipocytes) from precursor cells, and carefully controlling this process is therefore critical for health. This work examines this process mainly using cells that can be turned into adipocytes in the lab and studying the genes that regulate this process. Specifically we are focussing on a gene called BSCL2 which we know is critical for making fat tissue in humans as its disruption causes almost complete lack of fat. We have recently discovered that this gene regulates the process of adipocyte formation but the precise mechanism by which it does this is not clear. This work aims to define how BSCL2 controls the formation of fat cells, to identify the proteins it interacts with to do this, and how BSCL2 itself is regulated. In this way we will learn much more about how fat cells develop. This information will not only be critical for ultimately finding ways to treat patients with this very specific, rare but devastating form of lipodystrophy, but is also extremely relevant to understanding the development and treatment of obesity.