GASTRIC BYPASS EFFECTS ON MYOCARDIAL METABOLISM

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。肥胖影响超过4300万美国人，并与心力衰竭，猝死和心血管死亡的发病率增加有关。我们已经表明，增加肥胖，如测量的身体质量指数（BMI），是独立相关的左心室结构和功能的变化，特别是，向心性左心室重构和降低负荷的非依赖性措施的舒张和收缩功能和降低氧效率（心力衰竭的标志）。此外，我们已经表明，胰岛素抵抗，往往伴随着肥胖的心肌游离脂肪酸（FFA）代谢摄取（MFAUp），利用（MFAU）和氧化（MFAO）的独立相关的措施。此外，动物研究和初步人体研究的数据表明，心肌脂肪酸代谢过度与有害的心肌结构变化有关，并可能直接导致LV功能障碍。为了增加我们对BMI或胰岛素抵抗与人类心肌代谢、效率、结构和功能之间的这些关系的理解，我们建议研究胃旁路术诱导的体重减轻和随之而来的胰岛素抵抗改善对这些心肌变量的影响。我们进一步建议，以确定如何预期的变化，心肌脂肪酸代谢与全身FFA动力学和交付的变化。

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. Obesity affects more than 43 million Americans and is associated with an increased incidence of heart failure, sudden death, and cardiovascular death. We have shown that increasing obesity, as measured by body mass index (BMI), is independently associated with LV structural and functional changes, specifically, concentric LV remodeling and decreased load-independent measures of diastolic and systolic function and decreased oxygen efficiency (a hallmark of heart failure). Furthermore, we have shown that the insulin resistance that often accompanies obesity in independently related measures of myocardial free fatty acid (FFA) metabolism uptake (MFAUp), utilization (MFAU), and oxidation (MFAO). Moreover, there are data from animal studies and preliminary human studies that demonstrate that excessive myocardial fatty acid metabolism is linked to detrimental myocardial structural changes and may directly contribute to LV dysfunction. In order to increase our understanding of these relationships between BMI or insulin resistance and myocardial metabolism, efficiency, structure, and function in humans, we propose to study the effect of gastric bypass-induced weight loss and consequent improvement in insulin resistance on theses myocardial variables. We further propose to determine how the expected changes in myocardial fatty acid metabolism relate to changes in total body FFA kinetics and delivery.