Altered hepatic fatty acid metabolism in endotoxicosis: effect of L-carnitine on survival.
The activities of palmitoyl-coenzyme A (CoA) synthetase, carnitine acetyltransferase (CAT), and carnitine palmitoyltransferase (CPT) and the levels of ketone bodies, reduced coenzyme A (CoASH), carnitine, and their esters, which are involved in fatty acid metabolism, in rat liver and plasma were measured after the administration of Escherichia coli lipopolysaccharide (LPS). We also studied the effect of L-carnitine treatment before LPS administration on survival and on hepatic fatty acid metabolism. The activities of CAT and CPT and the concentrations of ketone bodies, CoA, and carnitine derivatives (except for malonyl-CoA) declined in the liver after LPS administration. The activity of palmitoyl-CoA synthetase was changed little after LPS administration, and the level of hepatic malonyl-CoA increased significantly, suggesting that LPS causes activated fatty acids to undergo esterification and lipogenesis rather than oxidation. Treatment of rats with L-carnitine before LPS greatly increased the survival rate, but did not affect enzymes that metabolize fatty acids, CoA, or carnitine derivatives in the liver. Further studies are necessary to elucidate the mechanism of the effect of carnitine on post-LPS survival.
Takeyama
N
N
Department of Critical Care Medicine, Kansai Medical University, Moriguchi, Japan.
Takagi
D
D
Matsuo
N
N
Kitazawa
Y
Y
Tanaka
T
T
D000818:Animals; D002331:Carnitine / Q000378:metabolism / Q000494:pharmacology*; D002332:Carnitine O-Acetyltransferase / Q000378:metabolism; D002334:Carnitine O-Palmitoyltransferase / Q000378:metabolism; D003065:Coenzyme A / Q000378:metabolism; D003066:Coenzyme A Ligases / Q000378:metabolism; D004926:Escherichia coli; D004951:Esterification; D005227:Fatty Acids / Q000378:metabolism*; D007657:Ketone Bodies / Q000378:metabolism; D008070:Lipopolysaccharides; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008316:Malonyl Coenzyme A / Q000378:metabolism; D010084:Oxidation-Reduction; D051381:Rats; D011919:Rats, Inbred Strains; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D012772:Shock, Septic / Q000378:metabolism*; D000098859:Long-Chain-Fatty-Acid-CoA Ligase
D005227:Fatty Acids; D007657:Ketone Bodies; D008070:Lipopolysaccharides; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D008316:Malonyl Coenzyme A; D002334:Carnitine O-Palmitoyltransferase; D002332:Carnitine O-Acetyltransferase; D003066:Coenzyme A Ligases; C090799:FAA2 protein, S cerevisiae; D000098859:Long-Chain-Fatty-Acid-CoA Ligase; D002331:Carnitine; D003065:Coenzyme A