Alpha-lipoic acid prevents lipotoxic cardiomyopathy in acyl CoA-synthase transgenic mice.
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.
Lee
Young
Y
Gifford Laboratories, Touchstone Center for Diabetes Research, University of Texas, Southwestern Medical Center, Dallas, TX 75390-8854, USA.
Naseem
R Haris
RH
Park
Byung-Hyun
BH
Garry
Daniel J
DJ
Richardson
James A
JA
Schaffer
Jean E
JE
Unger
Roger H
RH
D000818:Animals; D031204:Caloric Restriction; D002311:Cardiomyopathy, Dilated / Q000201:enzymology* / Q000235:genetics / Q000517:prevention & control*; D003066:Coenzyme A Ligases / Q000235:genetics / Q000378:metabolism*; D006321:Heart / Q000187:drug effects; D020738:Leptin / Q000097:blood; D051379:Mice; D008822:Mice, Transgenic; D009206:Myocardium / Q000201:enzymology / Q000473:pathology; D008063:Thioctic Acid / Q000627:therapeutic use*; D015533:Transcriptional Activation; D014280:Triglycerides / Q000097:blood / Q000378:metabolism*
D020738:Leptin; D014280:Triglycerides; D008063:Thioctic Acid; D003066:Coenzyme A Ligases