Contribution Of Myocyte Steatosis To Cardiac Dysfunction

描述（由申请人提供）：心肌脂质沉积增加是与肥胖和糖尿病相关的心肌病的特征。这项建议的长期目标是了解细胞内脂质沉积（脂肪变性）对心脏肥厚和心肌病发展的贡献。我们假设过量的细胞内脂质沉积导致心肌细胞脂毒性，进而导致代偿性肥大，在许多情况下，导致细胞损伤和细胞死亡。因此，具体目标是：

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.