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

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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.