{alpha}-Lipoic acid prevents lipotoxic cardiomyopathy in acyl CoA-synthase transgenic mice
- Gifford Laboratories, Touchstone Center for Diabetes Research, University of Texas, Southwestern Medical Center, Dallas, TX 75390-8854 (United States)
- Division of Cardiology, University of Texas, Southwestern Medical Center, Dallas, TX 75390-8854 (United States)
- Department of Internal Medicine, University of Texas, Southwestern Medical Center, Dallas, TX 75390-8854 (United States)
- Department of Pathology, University of Texas, Southwestern Medical Center, Dallas, TX 75390-8854 (United States)
- Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO 63110 (United States)
- Gifford Laboratories, Touchstone Center for Diabetes Research, University of Texas, Southwestern Medical Center, Dallas, TX 75390-8854 (United States) and Department of Internal Medicine, University of Texas, Southwestern Medical Center, Dallas, TX 75390-8854 (United States) and Veterans Affairs Medical Center, Dallas, TX 75216 (United States)
{alpha}-Lipoic acid ({alpha}-LA) mimics the hypothalamic actions of leptin on food intake, energy expenditure, and activation of AMP-activated protein kinase (AMPK). To determine if, like leptin, {alpha}-LA protects against cardiac lipotoxicity, {alpha}-LA was fed to transgenic mice with cardiomyocyte-specific overexpression of the acyl CoA synthase (ACS) gene. Untreated ACS-transgenic mice died prematurely with increased triacylglycerol content and dilated cardiomyopathy, impaired systolic function and myofiber disorganization, apoptosis, and interstitial fibrosis on microscopy. In {alpha}-LA-treated ACS-transgenic mice heart size, echocardiogram and TG content were normal. Plasma TG fell 50%, hepatic-activated phospho-AMPK rose 6-fold, sterol regulatory element-binding protein-1c declined 50%, and peroxisome proliferator-activated receptor-{gamma} cofactor-1{alpha} mRNA rose 4-fold. Since food restriction did not prevent lipotoxicity, we conclude that {alpha}-LA treatment, like hyperleptinemia, protects the heart of ACS-transgenic mice from lipotoxicity.
- OSTI ID:
- 20798978
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 344, Issue 1; Other Information: DOI: 10.1016/j.bbrc.2006.03.062; PII: S0006-291X(06)00537-7; Copyright (c) 2006 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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