Contribution Of Myocyte Steatosis To Cardiac Dysfunction

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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.