The role of wnt signalling network in adipose tissue development and plasticity

肥胖和糖尿病在西方世界变得越来越普遍。肥胖和糖尿病患者在心脏病发作时过早死亡的风险很高。因此，肥胖和相关的代谢性疾病是一个重大的公共卫生问题。理想的策略是防止个人变得肥胖，但很明显，目前的努力在遏制这种流行病方面是无效的。通过增加我们对正常脂肪组织如何发展和调整其大小以应对环境变化的理解，我们可能会找到更有效的策略，在体重增加的情况下保持健康。我们认为脂肪组织储存脂肪的能力不是无限的，当超过这个水平时，就会出现临床问题。我们的研究目的是鉴定和研究一组与组织发育和改变脂肪细胞形成程序相关的蛋白质（Wnts）。这些蛋白质可以作为信使来控制新脂肪组织的大小和招募。这些蛋白质如何在人体脂肪组织中引起这些变化尚不清楚。我们已经证明关键的Wnt信号分子在人类脂肪细胞形成中是协调调节的。我们还在一个肥胖个体中发现了这些分子中的一种人类突变。这种突变似乎使分子信号缺陷，可能与他们的肥胖有关。在此，我们建议鉴定和表征这些分子的完整补体，并确定它们在肥胖和脂肪细胞发育的特定实验模型中改变脂肪组织大小的作用。我们还将生成一个新的模型，使我们能够研究这种新的wnt突变体在全身能量储存中的作用。我们假设wnt信号网络协调脂肪细胞招募和大小之间的平衡。该网络的改变可能导致脂肪组织大小和细胞数量的增加，最终可能产生重要的代谢后果。

Obesity and diabetes are becoming increasingly prevalent in the western world. Individuals that are obese and diabetic are at high risk of dying at an early age from heart attacks. Hence, obesity and the related metabolic diseases represent a significant public health issue. The ideal strategy would be to prevent individuals from becoming obese, but it is clear that current efforts have been ineffective at curbing this epidemic. By increasing our understanding of how normal fat tissue develops and adjusts its size in response to environmental changes, we may identify more effective strategies for maintaining their health despite increased body weight. We think that adipose tissue does not have an unlimited capacity to store fat and it is when this level is surpassed that clinical problems arise. Our research aims to identify and study a group of proteins (Wnts) that are related to tissue development and alter the program of fat cell formation. These proteins can act as messengers to control the size and recruitment of new fat tissue. How these proteins bring about these changes in human fat tissue remains unclear. We have shown that key Wnt signalling molecules are co-ordinately regulated in human fat cell formation. We have also identified a human mutation in one of these molecules, in an obese individual. This mutation appears to render the molecule signalling defective and may be related to their obesity. Herein, we propose to identify and characterise the full complement of these molecules and identify their roles in altering fat tissue size in specific experimental models of obesity and fat cell development. We will also generate a new model that will allow us to investigate the role of this novel wnt mutant in whole body energy storage. We hypothesise that the wnt signalling network orchestrates the balance between fat cell recruitment and size. Alterations in this network may result in increased fat tissue size and cell number that ultimately may have important metabolic consequences.