title: Alpha-lipoic acid prevents lipotoxic cardiomyopathy in acyl CoA-synthase transgenic mice.
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.
authors.affiliation: Gifford Laboratories, Touchstone Center for Diabetes Research, University of Texas, Southwestern Medical Center, Dallas, TX 75390-8854, USA.
authors.forename: Young
authors.initials: Y
authors.lastname: Lee
authors.forename: R Haris
authors.initials: RH
authors.lastname: Naseem
authors.forename: Byung-Hyun
authors.initials: BH
authors.lastname: Park
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Garry
authors.forename: James A
authors.initials: JA
authors.lastname: Richardson
authors.forename: Jean E
authors.initials: JE
authors.lastname: Schaffer
authors.forename: Roger H
authors.initials: RH
authors.lastname: Unger
mesh_terms: 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*
chemical_list: D020738:Leptin; D014280:Triglycerides; D008063:Thioctic Acid; D003066:Coenzyme A Ligases