Mechanisms in Disorders of Energy Balance

我们的目标是了解控制我们吃什么以及我们如何储存和使用能量的生物过程。这些途径在肥胖和相关代谢疾病（如2型糖尿病）中受到干扰。这些知识最终将导致这些疾病的新治疗方法的发展。我们知道，一个人的基因构成在决定患肥胖症的易感性及其有害后果方面起着重要作用。最近的进展使分析人类遗传密码变得更加容易。我们的目标是利用人类基因研究的数据来获得导致人类肥胖的基本见解，并建议将这些基因研究与基于细胞系和整个动物模型的实验室研究结合起来，以更好地了解所涉及的途径。该项目建立在我们之前的工作基础上，研究对象是来自世界各地的一大批儿童时期严重肥胖的患者，并为随后关于食物摄入和能量使用的详细研究奠定了基础。虽然人类将永远是我们选择的实验对象，但有一些重要的机械问题需要替代方法。我们将使用啮齿动物模型来探索在人类中无法轻易解决的疾病过程的各个方面。此外，啮齿类动物的优势是容易受到基因操纵的影响，从而允许对特定基因进行精确的改变，重要的是，可以创建相关的、特定的人类疾病的动物模型。

We aim to understand the biological processes controlling what we eat and how we store and use energy. These pathways are disturbed in obesity and related metabolic conditions such as Type 2 diabetes. This knowledge will, ultimately, lead to development of new treatments for these disorders.We know that an individual’s genetic make-up has a significant role in determining susceptibility to developing obesity and its deleterious consequences. Recent advances have made it substantially easier to analyse human genetic code. We aim to exploit data from human genetic studies to gain fundamental insights into what causes human obesity, and propose to combine these genetic studies with laboratory studies based around cell lines and whole animal models to better understand the pathways involved.This programme builds on our previous work centred around a large group of patients from around the world who developed severe obesity as children and formed the basis for subsequent detailed studies on food intake and energy use. While humans will always be our experimental subject of choice, there are important mechanistic questions that require alternative approaches. We will use rodent models to explore aspects of disease processes that cannot be readily addressed in humans. Further, rodents have the advantage of being readily susceptible to genetic manipulation allowing precise alteration of specific genes and, importantly, creation of animal models of relevant, specific, human diseases.