Lipotoxic heart disease in obese rats: implications for human obesity

YT Zhou, P Grayburn, A Karim… - Proceedings of the …, 2000 - National Acad Sciences
YT Zhou, P Grayburn, A Karim, M Shimabukuro, M Higa, D Baetens, L Orci, RH Unger
Proceedings of the National Academy of Sciences, 2000National Acad Sciences
To determine the mechanism of the cardiac dilatation and reduced contractility of obese
Zucker Diabetic Fatty rats, myocardial triacylglycerol (TG) was assayed chemically and
morphologically. TG was high because of underexpression of fatty acid oxidative enzymes
and their transcription factor, peroxisome proliferator-activated receptor-α. Levels of
ceramide, a mediator of apoptosis, were 2–3 times those of controls and inducible nitric
oxide synthase levels were 4 times greater than normal. Myocardial DNA laddering, an …
To determine the mechanism of the cardiac dilatation and reduced contractility of obese Zucker Diabetic Fatty rats, myocardial triacylglycerol (TG) was assayed chemically and morphologically. TG was high because of underexpression of fatty acid oxidative enzymes and their transcription factor, peroxisome proliferator-activated receptor-α. Levels of ceramide, a mediator of apoptosis, were 2–3 times those of controls and inducible nitric oxide synthase levels were 4 times greater than normal. Myocardial DNA laddering, an index of apoptosis, reached 20 times the normal level. Troglitazone therapy lowered myocardial TG and ceramide and completely prevented DNA laddering and loss of cardiac function. In this paper, we conclude that cardiac dysfunction in obesity is caused by lipoapoptosis and is prevented by reducing cardiac lipids.
National Acad Sciences