FATTY ACID OXIDATION IN ISOLATED PERFUSED MOUSE HEART

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。心脏生理学的一个中心问题是确定能量产生的来源。许多研究已经测量了心脏可用的每种外源性底物的氧化，并且通常得出结论，长链脂肪酸是氧化的优选底物，在生理条件下贡献了60-70%的乙酰辅酶A产生。能量产生的其余部分取决于替代底物的浓度和神经体液条件。然而，了解心脏脂肪酸代谢的一个基本困难是，内源性甘油三酯库也可能有助于能量产生。甘油三酯含量在缺血性心脏、糖尿病心脏和肥大心脏中是异常的，但直到最近，甘油三酯被认为是长链脂肪酸的相对惰性储存，在正常生理或疾病中几乎没有作用。现在有越来越多的兴趣的可能性，即肌细胞内甘油三酯通过刺激细胞凋亡在2型糖尿病患者左心室功能受损的发病机制中发挥核心作用。然而，几乎没有什么是已知的动力学的甘油三酯周转和外源性长链脂肪酸交换与甘油三酯存储的程度，同时作为一个关键的能源生产。

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. A central problem in cardiac physiology is to determine the sources of energy production. Many studies have measured oxidation of each exogenous substrate available to the heart and have generally concluded that long chain fatty acids are the preferred substrate for oxidation, contributing 60-70% of acetyl-CoA production under physiological conditions. The remainder of energy production depends on the concentration of alternative substrates and neurohumoral conditions. However, a basic difficulty in understanding cardiac metabolism of fatty acids is that the endogenous triglyceride pool may also contribute to energy production. Triglyceride content is abnormal in ischemic, diabetic and hypertrophied hearts, yet until recently triglycerides were thought to function as relatively inert stores of long chain fatty acids with little role in either normal physiology or disease. There is now increasing interest in the possibility that intramyocellular triglycerides play a central role in the pathogenesis of impaired left ventricular function among patients with type 2 diabetes via stimulation of apoptosis. However, almost nothing is known about the kinetics of triglyceride turnover and the extent to which exogenous long chain fatty acids exchange with triglyceride stores while simultaneously serving as a critical source for energy production.