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 language||English (US)|
|Number of pages||7|
|Journal||Biochemical and Biophysical Research Communications|
|State||Published - May 26 2006|
Bibliographical noteFunding Information:
This study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases-002700, the Department of Veterans Affairs Merit Award, the Juvenile Diabetes Research Foundation, Takeda Pharmaceuticals North America, Inc., the Jensen Charitable Lead Trust, (R.H.U.), and the American Diabetes Association (J.E.S.).
- Fatty heart
- Lipotoxic cardiomyopathy
- Metabolic syndrome
- α-Lipoic acid