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

鉴于肥胖率高且不断上升，过量脂肪对健康的有害影响是众所周知的。然而，脂肪量异常低（脂肪营养不良）的情况非常罕见，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，重要的是要发展适量的脂肪，并使其能够有效地储存和释放营养物质，并分泌它适当产生的激素。增加脂肪量涉及从前体细胞制造新的脂肪细胞（脂肪细胞），因此仔细控制这一过程对健康至关重要。这项工作主要使用可以在实验室中转化为脂肪细胞的细胞来研究这一过程，并研究调节这一过程的基因。具体来说，我们正在关注一种名为BSCL 2的基因，我们知道它对人类脂肪组织的形成至关重要，因为它的破坏导致几乎完全缺乏脂肪。我们最近发现该基因调节脂肪细胞形成的过程，但其确切机制尚不清楚。这项工作的目的是确定BSCL 2如何控制脂肪细胞的形成，确定与之相互作用的蛋白质，以及BSCL 2本身是如何调节的。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代谢障碍患者的方法至关重要，而且对于了解肥胖的发展和治疗也非常重要。

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.