Inherited defects in the mitochondrial fatty acid oxidation pathway can lead to lipotoxic cardiomyopathy and sudden death in children and young adults. The exact chain of pathologic events remains unknown, but in the 1 April Journal of Clinical Investigation Hsiu-Chiang Chiu and colleagues from Washington University School of Medicine describe the development of a murine model of metabolic cardiomyopathy. The study also suggests that lipotoxic cardiomyopathy is based on a mismatch between myocardial fatty acid uptake and utilization.

Chiu et al generated a transgenic mouse line that overexpresses long-chain acyl-CoA synthetase in the heart, a protein important in the vectorial fatty acid transport across the plasma membrane. The mice showed cardiac myocyte triglyceride accumulation that was associated with cardiac dysfunction and premature death similar to lipotoxic cardiomyopathy. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling staining and cytochrome c release in transgenic hearts showed that lipid-induced programmed cell death caused the cardiac...

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