[unreadable] We have assembled the best investigators and technology at the UT Southwestern Medical Center at Dallas to focus on a major medical problem in the U.S.-- obesity and the metabolic syndrome. This application will create mechanisms to bring together diverse groups of investigators to investigate the behavioral, metabolic, and molecular events that cause obesity and the metabolic syndrome. The major focus of this effort will be on the brain and liver, organs that both play central roles in the development of obesity and its adverse metabolic consequences. Our goals are to better understand how the brain regulates food intake and energy expenditure and to reveal how dysregulation of glucose and lipid metabolism in the liver contributes to the development of the metabolic syndrome. To address these objectives, we have developed four research teams that vary in approaches and expertise who will interact extensively to pursue the shared goals of this project. Collaborations among investigators will occur on two levels. Within each team, extensive exchanges between investigators will foster direct collaborative efforts. Interactions will also occur between the four major teams to capitalize on the diverse expertise within each of the four groups and to provide comprehensive approaches to our major objectives. To achieve these goals, we have established the Taskforce for Obesity Research at Southwestern (TORS). TORS will cement bonds among the traditionally disparate disciplines of neuroendocrinology, genetics, lipid metabolism, intermediary metabolism, and clinical epidemiology into a cohesive center to study obesity and the metabolic syndrome. Over the next three years, the major objectives will be to: 1) develop a program to foster interdisciplinary interactions at UT Southwestern to study obesity and the metabolic syndrome; 2) develop a state-of-the-art program to elucidate the metabolic and molecular basis of obesity and the metabolic syndrome using genetically modified mice; and 3) support the translation of scientific findings made in animal models to humans. [unreadable] [unreadable]