α-Lipoic acid prevents lipotoxic cardiomyopathy in acyl CoA-synthase transgenic mice

Young H Lee, R. Haris Naseem, Byung Hyun Park, Daniel J. Garry, James A Richardson, Jean E. Schaffer, Roger H Unger

Research output: Contribution to journalArticlepeer-review

67 Scopus citations

Abstract

α-Lipoic acid (α-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, α-LA protects against cardiac lipotoxicity, α-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 α-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-γ cofactor-1α mRNA rose 4-fold. Since food restriction did not prevent lipotoxicity, we conclude that α-LA treatment, like hyperleptinemia, protects the heart of ACS-transgenic mice from lipotoxicity.

Original languageEnglish (US)
Pages (from-to)446-452
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume344
Issue number1
DOIs
StatePublished - May 26 2006

Keywords

  • Fatty heart
  • Leptinomimetic
  • Lipotoxic cardiomyopathy
  • Metabolic syndrome
  • α-Lipoic acid

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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