MYOCARDIAL SUBSTRATE SELECTION AND SWITCHING IN LEAN AND OBESE HUMANS

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 心肌有能力在游离脂肪酸和葡萄糖作为氧化底物之间切换，以响应底物供应、工作需求以及局部和全身调节剂的变化。肥胖和糖尿病等代谢紊乱与心肌功能障碍发生率增加有关，燃料选择的改变可能是这种关系的基础。关于基础状态下的心肌燃料选择以及这些疾病状态下对胰岛素的反应知之甚少。目前的提案将检验以下假设：在肥胖的胰岛素抵抗受试者中，脂肪酸对整体心肌代谢的贡献增加，并且在胰岛素刺激下转向葡萄糖代谢的能力降低。在当前协议中，我们将对瘦和肥胖受试者的心肌脂肪酸氧化、总氧化和组织灌注进行正电子发射断层扫描测量。这些研究将在基础禁食条件下和高胰岛素血症的稳态条件下进行。由此产生的数据将用于支持未来的拨款提案，该提案将更详细地探讨这些问题。

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. The myocardium has the capacity to switch between free fatty acids and glucose as oxidative substrates, in response to changes in substrate supply, work demand, and local and systemic regulators. Disorders of metabolism, such as obesity and diabetes, are associated with increased rates of myocardial dysfunction, and it is possible that alterations in fuel selection underlie this relationship. Comparatively little is known about myocardial fuel selection in the basal state and in response to insulin in these disease states. The current proposal will test the hypothesis that the contribution of fatty acids to overall myocardial metabolism is increased in obese insulin resistant subjects, and that the capacity to switch to glucose metabolism under insulin stimulation is reduced. In the current protocol, we will perform positron emission tomography measurements of myocardial fatty acid oxidation, total oxidation, and tissue perfusion in lean and obese subjects. These studies will be performed under basal fasting conditions, and under steady state conditions of hyperinsulinemia. The resulting data will be used to support a future grant proposal which will explore these questions in more detail.