This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This is a new project stimulated by the P20 proposal. This support is bringing together diverse groups of investigators at UT Southwestern 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. Over the long term, we envision a set of clinical research protocols involving systemic administration of 13C and 2H to determine the kinetics of whole-body glucose production, hepatic fatty acid oxidation, etc., which are fundamental to understanding the physiology of insulin-resistant states. Simultaneously, organ-specific MR imaging and spectroscopy can be used to probe metabolism in critical organs such as skeletal muscle and liver. Based on our success with stable isotope analysis of metabolism plus our recent progress with magnetization transfer contrast agents (PARACEST agents), this goal can be achieved in experimental animals, and initial development will be carried out in human subjects.
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