{alpha}-Lipoic acid prevents lipotoxic cardiomyopathy in acyl CoA-synthase transgenic mice

• Published in: Biochemical and biophysical research communications Vol. 344; no. 1
• Main Authors: Lee, Young, Department of Internal Medicine, University of Texas, Southwestern Medical Center, Dallas, TX 75390-8854, Naseem, R. Haris, Park, Byung-Hyun, Garry, Daniel J., Richardson, James A., Schaffer, Jean E., Unger, Roger H.
• Format: Journal Article
• Language: English
• Published: United States 26.05.2006
• Subjects: 60 APPLIED LIFE SCIENCES; AMP; APOPTOSIS; FIBROSIS; FOOD; GENES; HEART; INTAKE; LEPTIN; LIVER; MICROSCOPY; RECEPTORS; STEROLS; TRANSGENIC MICE
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2006.03.062

{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.