Carnitine regulates myocardial metabolism by Peroxisome Proliferator-Activated Receptor-alpha (PPARalpha) in alcoholic cardiomyopathy
Ling Jing, Li-jun Zhou, Wei-min Li, Feng-min Zhang, Lin Yuan, Shuang Li, Jian Song, Ying Sang
Med Sci Monit 2011; 17(1): BR1-9
Background: Chronic alcohol intake exerts myocardial damage en route to the development of alcoholic cardiomyopathy (ACM), although the precise pathogenesis of ACM is unknown. Carnitine is known to participate in the regulation of metabolism in a number of heart diseases. This study was designed to examine the interplay between myocardial metabolism and carnitine in the development of ACM.
Material/Methods: Experimental animals were divided into 3 groups: (i) group A: alcohol-fed. (ii) group B: alcohol/carnitine: (200mg/kg/d, p.o. by mixing carnitine in rat chow). (iii) group C: control. Blood levels of free fatty acid (FFA), total carnitine (TC) and free carnitine (FC) were monitored in rats receiving alcohol with or without carnitine. Mitochondrial adenine nucleotide translocator-1 (ANT1) activity, ATPase activity, high energy phosphate concentration, peroxisome proliferator-activated receptor-α (PPARα), carnitine-palmitoyl transferase I (CPT-I), medium-chain acyl-coenzyme A dehydrogenase (MCAD), ANT1 and ATPase mRNA and protein expression were also monitored in myocardial tissue.
Results: Experimental animals received alcohol with or without carnitine for six6 months. Our results indicated that FFA increased abruptly. TC and FC were significantly decreased in groups receiving alcohol at 4 months. The concentration of ATP, ADP and AMP in the myocardium decreased following 2 months of alcohol administration. mRNA and protein expression of PPARα, CPT-I, MCAD, ANT1 and ATPase expressions were gradually altered in groups following alcohol feeding.
Conclusions: These observations suggest that abnormal metabolism is present in the myocardium during the development of ACM. Carnitine may improve myocardial metabolism by elevating the content of PPARα, CPT-I and MCAD.
Keywords: Microscopy, Electron, Ethanol, Fatty Acids, Nonesterified - blood, Carnitine O-Palmitoyltransferase - metabolism, Carnitine - pharmacology, Cardiomyopathy, Alcoholic - metabolism, Animals, Adenosine Triphosphate - metabolism, Adenosine Triphosphatases - metabolism, Adenosine Monophosphate - metabolism, Adenosine Diphosphate - metabolism, Adenine Nucleotide Translocator 1 - metabolism, Acyl-CoA Dehydrogenase - metabolism, Myocardium - ultrastructure, PPAR alpha - metabolism, Phosphates - metabolism, Rats