TASK FORCE FOR OBESITY RESEARCH AT SOUTHWESTERN - P20

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。这是一个由P20提案推动的新项目。这项支持将德克萨斯大学西南分校的不同研究小组聚集在一起，研究导致肥胖和代谢综合征的行为、代谢和分子事件。这项工作的主要重点将放在大脑和肝脏上，这两个器官在肥胖及其不良代谢后果的发展中都起着核心作用。我们的目标是更好地了解大脑是如何调节食物摄入和能量消耗的，并揭示肝脏中葡萄糖和脂质代谢失调是如何导致代谢综合征的发展的。从长远来看，我们设想了一套临床研究方案，包括全身给药13C和2H，以确定全身葡萄糖产生的动力学，肝脂肪酸氧化等，这是理解胰岛素抵抗状态生理学的基础。同时，器官特异性磁共振成像和光谱学可用于探测骨骼肌和肝脏等关键器官的代谢。基于我们在代谢稳定同位素分析方面的成功以及我们在磁化转移造影剂（PARACEST剂）方面的最新进展，这一目标可以在实验动物中实现，并将在人体受试者中进行初步开发。

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.