Paradoxical role of lipid metabolism in heart function and dysfunction.
The heart utilizes fatty acids as a substrate in preference to glucose for the production of energy. The rate of fatty acid uptake and oxidation by heart muscle is controlled by the availability of exogenous fatty acids, the rate of acyl translocation across the mitochondrial membrane and the rate of acetyl-CoA oxidation by the citric acid cycle. Carnitine acyl-CoA transferase appears to have an important function in coupling the fatty acid activation and acyl transfer to the oxidative phosphorylation. Activated fatty acids are also utilized for the synthesis of triglycerides and membrane phospholipids in the myocardium. The inhibition of long chain acyl-carnitine transferase I reduces the oxidation of fatty acids and promotes the synthesis of lipids in the myocardium. Accumulation of fatty acids and their metabolites such as long chain acyl-CoA and long chain acyl-carnitine has been associated with cardiac dysfunction and cell damage in both ischemic and diabetic hearts. Alterations in the composition of membrane phospholipids are also considered to change the activities of various membrane bound enzymes and subsequently heart function under different pathophysiological conditions. Chronic diabetes was found to be associated with increased plasma lipids, subcellular defects and cardiac dysfunction. Lowering the plasma lipids or reducing the oxidation of fatty acids by agents such as etomoxir, an inhibitor of palmitoylcarnitine transferase I was found to promote glucose utilization and remodel the subcellular membranous organelles in the heart.(ABSTRACT TRUNCATED AT 250 WORDS)
Dhalla
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NS
Division of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, Winnipeg, Manitoba, Canada.
Elimban
V
V
Rupp
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H
D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D002331:Carnitine / Q000502:physiology; D048909:Diabetes Complications; D003920:Diabetes Mellitus / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000378:metabolism; D004041:Dietary Fats / Q000009:adverse effects / Q000378:metabolism; D004734:Energy Metabolism; D005227:Fatty Acids / Q000009:adverse effects / Q000378:metabolism; D006321:Heart / Q000502:physiology*; D006331:Heart Diseases / Q000209:etiology / Q000378:metabolism*; D006801:Humans; D006949:Hyperlipidemias / Q000150:complications; D050356:Lipid Metabolism; D009206:Myocardium / Q000378:metabolism*; D010743:Phospholipids / Q000378:metabolism; D051381:Rats
D004041:Dietary Fats; D005227:Fatty Acids; D010743:Phospholipids; D000251:Adenosine Triphosphatases; D002331:Carnitine