MYOCARDIAL TRIGLYCERIDE AND LV PERFORMANCE ASSESS BY MRS AND MRI

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 传统上，肥胖被认为是心脏病的间接原因。 肥胖个体通常存在许多传统的易患心肌梗死和缺血性心肌病的危险因素（高血压、血脂异常和2型糖尿病）。除了Fracture风险评分升高外，肥胖的血流动力学标志是高动力循环（心率和每搏输出量增加）。这被认为是以牺牲偏心性左心室重构为代价对脂肪量增加的代偿性适应。 在极度肥胖症中，高动力循环发展为非缺血性扩张型心肌病。 与这些相当传统的概念相反，一个新兴的基础研究机构重新审视了一个假设，即脂肪是一种直接的心脏毒素。 在健康条件下，大多数甘油三酸酯储存在脂肪细胞中，而储存在非脂肪细胞组织（如胰腺、肝脏、骨骼肌和心肌）中的甘油三酸酯的量是最小的，并且受到非常严格的调节。 当这种调节被破坏时，胞质甘油三酯在这些器官中过度积累（“脂肪变性”），并参与激活不良信号级联，最终导致不可逆的细胞死亡（“脂毒性”），导致几种公认的临床综合征。 这些包括非酒精性脂肪性肝炎（NASH），2型糖尿病中的胰腺β细胞衰竭和扩张型心肌病。 我们实验室的初步研究表明，人类肥胖和2型糖尿病的特征是心肌甘油三酯水平升高;然而，心肌甘油三酯水平和心脏性能之间的关系尚不清楚。 因此，本提案的主要目的是确定心肌甘油三酯含量对人类左心室性能的影响。

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. Traditionally, obesity is considered an indirect cause of heart disease. Obese individuals typically present with a number of traditional Framingham risk factors, (hypertension, dyslipidemia, and type 2 diabetes) predisposing them to myocardial infarction and ischemic cardiomyopathy. In addition to an elevated Framingham risk score, the hemodynamic hallmark of obesity is a hyperdynamic circulation (increased heart rate and stroke volume). It is thought to be a compensatory adaptation to increased adipose mass at the expense of eccentric left ventricular remodeling. In extreme obesity hyperdynamic circulation progresses to non-ischemic dilated cardiomyopathy. In contrast to these rather traditional concepts, an emerging body of basic research revisits a hypothesis that fat is a direct cardiotoxin. Under healthy conditions, most trigylceride is stored in adipocytes while the amount of triglyceride stored in non-adipocyte tissues (such as the pancreas, the liver, skeletal muscle, and the myocardium) is minimal and very tightly regulated. When this regulation is disrupted, cytosolic triglyceride accumulates excessively in these organs ("steatosis") and has been implicated in activating adverse signaling cascades culminating in irreversible cell death ("lipotoxicity"), leading to several well-recognized clinical syndromes. These include non-alcoholic steatohepatitis (NASH), pancreatic beta-cell failure in type 2 diabetes, and dilated cardiomyopathy. Initial studies in our laboratory revealed that human obesity and type 2 diabetes are characterized by elevated myocardial triglyceride levels; however, the relationship between myocardial triglyceride levels and cardiac performance remains unclear. The primary aim of this proposal is therefore to determine the influence of myocardial triglyceride content on left ventricular performance in humans.