1. α-Lipoic acid prevents lipotoxic cardiomyopathy in acyl CoA-synthase transgenic mice
- Author
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Young H Lee, Byung Hyun Park, Jean E. Schaffer, R. Haris Naseem, Roger H Unger, James A. Richardson, and Daniel J. Garry
- Subjects
Cardiomyopathy, Dilated ,Leptin ,Transcriptional Activation ,Genetically modified mouse ,medicine.medical_specialty ,Transgene ,Biophysics ,Cardiomyopathy ,Mice, Transgenic ,Biology ,Biochemistry ,Mice ,chemistry.chemical_compound ,Fibrosis ,Internal medicine ,Coenzyme A Ligases ,medicine ,Animals ,Molecular Biology ,Triglycerides ,Caloric Restriction ,Thioctic Acid ,Myocardium ,AMPK ,Heart ,Cell Biology ,medicine.disease ,Lipoic acid ,Endocrinology ,Lipotoxicity ,chemistry - Abstract
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-1alpha 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.
- Published
- 2006
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