期刊
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
卷 344, 期 1, 页码 446-452出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2006.03.062
关键词
leptinomimetic; lipotoxic cardiomyopathy; alpha-lipoic acid; metabolic syndrome; fatty heart
资金
- PHS HHS [002700] Funding Source: Medline
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 red 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 of.-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-1 alpha 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. Published by Elsevier Inc.
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