GASTRIC BYPASS EFFECTS ON MYOCARDIAL METABOLISM

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。肥胖影响了4300多万美国人，并与心力衰竭、猝死和心血管死亡的发生率增加有关。我们已经表明，体重指数（BMI）测量的肥胖增加与左室结构和功能变化独立相关，特别是，同心左室重塑和舒张和收缩功能的负荷独立测量降低以及氧效率降低（心力衰竭的标志）。此外，我们已经表明，经常伴随肥胖的胰岛素抵抗与心肌游离脂肪酸（FFA）代谢摄取（MFAUp）、利用（MFAU）和氧化（MFAO）的独立相关指标有关。此外，动物研究和初步人体研究的数据表明，心肌脂肪酸代谢过多与有害的心肌结构改变有关，并可能直接导致左室功能障碍。为了进一步了解BMI或胰岛素抵抗与人类心肌代谢、效率、结构和功能之间的关系，我们建议研究胃分流术诱导的体重减轻及其对胰岛素抵抗的改善对这些心肌变量的影响。我们进一步建议确定心肌脂肪酸代谢的预期变化与全身FFA动力学和递送的变化之间的关系。

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.