Mechanisms in Disorders of Energy Balance

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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.