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 journalArticle

61 Citations (Scopus)

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

Fingerprint

Thioctic Acid
Acyl Coenzyme A
Cardiomyopathies
Transgenic Mice
AMP-Activated Protein Kinases
Leptin
Sterol Regulatory Element Binding Protein 1
Peroxisome Proliferator-Activated Receptors
Dilated Cardiomyopathy
Cardiac Myocytes
Energy Metabolism
Microscopy
Microscopic examination
Triglycerides
Fibrosis
Eating
Genes
Chemical activation
Apoptosis
Plasmas

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

α-Lipoic acid prevents lipotoxic cardiomyopathy in acyl CoA-synthase transgenic mice. / Lee, Young H; Naseem, R. Haris; Park, Byung Hyun; Garry, Daniel J.; Richardson, James A; Schaffer, Jean E.; Unger, Roger H.

In: Biochemical and Biophysical Research Communications, Vol. 344, No. 1, 26.05.2006, p. 446-452.

Research output: Contribution to journalArticle

Lee, Young H ; Naseem, R. Haris ; Park, Byung Hyun ; Garry, Daniel J. ; Richardson, James A ; Schaffer, Jean E. ; Unger, Roger H. / α-Lipoic acid prevents lipotoxic cardiomyopathy in acyl CoA-synthase transgenic mice. In: Biochemical and Biophysical Research Communications. 2006 ; Vol. 344, No. 1. pp. 446-452.
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