Obesity is a global epidemic. The number of people who are obese or overweight increases annually. Being obese or overweight significantly increases the risk of co-morbidities that are currently amongst the major health problems of modern times, including diabetes and cardiovascular disease, collectively known as the metabolic syndrome. Currently 2-7% of European healthcare budgets are consumed addressing health problems arising from excess body weight, and this is predicted to increase. Body weight regulation is complex. In order to find successful therapeutic interventions it is essential that we understand the molecular basis and mechanisms of appetite and energy balance regulation. For decades thyroid hormone deficiency has been known to cause obesity. It has been assumed that the principal cause of obesity by hypothyroidism is reduced energy expenditure in peripheral tissues. But there is now compelling evidence that thyroid hormone has a direct role in regulating neural mechanisms involved appetite and energy expenditure. The objectives of this project are 1. To show that T3 chronically released in the hypothalamus of the rat causes increased food intake, body weight with potential to develop into metabolic syndrome. 2. To identify thyroid hormone-regulated genes involved in hypothalamic control of appetite and energy balance. These objectives will be met by using state-of-the-art approaches including brain implant technology and microarray analysis of hypothalamic gene expression. The work will be carried out at the University of Aberdeen Rowett Institute of Health and Nutrition, an institute with a wealth of experience in nutrition research. The project is expected to provide significant new information on involvement and mechanism of thyroid hormone in appetite and energy balance, and to contribute to priorities identified in EU work programmes of FP5, FP6 and the current FP7 work programme for Health.