Contribution Of Myocyte Steatosis To Cardiac Dysfunction

描述（由申请人提供）：心肌脂质沉积增加是肥胖和糖尿病相关心肌病的特征。这项计划的长期目标是了解细胞内脂质沉积（脂肪变性）对心脏肥大和心肌病发展的作用。我们推测，细胞内脂质沉积过多导致心肌细胞的脂毒性，这反过来又导致代偿性肥大，在许多情况下，细胞损伤和细胞死亡。因此，具体目标是： 1.检测甘油三酯蓄积（脂肪变性）对新生大鼠心室肌细胞肥大和凋亡的影响。 2.使用心脏限制性二酰基甘油酰基转移酶过度表达的小鼠模型检查甘油三酯蓄积对心脏结构和功能的影响。

DESCRIPTION (provided by applicant): Increased myocardial lipid deposition is a feature of the cardiomyopathy associated with obesity and diabetes mellitus. The long-term objective of this proposal is to understand the contribution of intracellular lipid deposition (steatosis) to the development of cardiac hypertrophy and cardiomyopathy. We hypothesize that excessive intracellular lipid deposition leads to lipotoxicity of the cardiac myocyte, which, in turn, results in compensatory hypertrophy and, in many instances, cell damage and cell death. Accordingly, the specific aims are to: 1. Examine the effects of triglyceride accumulation (steatosis) on hypertrophy and apoptosis in neonatal rat ventricular myocytes. 2. Examine the effect of triglyceride accumulation on cardiac structure and function using a murine model of cardiac-restricted over expression of diacylglycerol acyltransferase.