Obesity is a major contributor to hypertension and heart disease. Elevated blood lipids accumulate in peripheral tissues such as the heart, causing deleterious effects on tissue function, a condition known as lipotoxicity. Lim et al. used Drosophila to identify a novel pathway leading to obesity-induced cardiac lipotoxicity that is independent of excess caloric intake but involves dysregulated membrane phospholipid homeostasis. They report that the easily shocked (eas) mutant, which is defective in the synthesis of the abundant membrane phospholipid phosphatidylethanolamine (PE), exhibits elevated triglyceride levels in the heart, tachycardia (accelerated heart rate), cardiac constriction (akin to restrictive cardiomyopathy), and is prone to cardiac arrest and fibrillation under stress conditions. PE deficiency overactivates the Drosophila sterol regulatory element-binding protein (dSREBP) lipogenic pathway, which globally regulates lipid homeostasis. Suppressing the dSREBP pathway in eas hearts rescues the cardiac defects and normalises triglyceride levels. These results support the hypothesis that phospholipid homeostasis and cardiac lipotoxicity are molecularly linked, and further our understanding of obesity-related disease pathogenesis.

Lim H. Y., Wang W., Wessells R. J., Ocorr K., Bodmer R. (2011). Phospholipid homeostasis regulates lipid metabolism and cardiac function through SREBP signaling in Drosophila. Genes. Dev. 25, 189– 200.
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Written by editorial staff. © 2011. Published by The Company of Biologists Ltd.
2011
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