Changes of hepatic fatty acid metabolism produced by chronic thioacetamide administration in rats

Hepatology. 1992 Jun;15(6):1099-106. doi: 10.1002/hep.1840150621.


Hepatic mitochondrial functions related to fatty acid metabolism, including the respiratory control ratio, fatty acid oxidative capacity and carnitine palmitoyltransferase I activity, were studied in vitro with mitochondria isolated from rats treated with thioacetamide for up to 12 wk. The levels of ketone bodies, carnitine, carnitine esters and malonyl-coenzyme A were also determined in liver extracts. Polarography of mitochondrial respiration from succinate or glutamate plus malate showed a lower respiratory control ratio in thioacetamide-treated rats, whereas uncoupled oxygen consumption was not altered. This suggests that the mitochondrial respiratory chain capacity remained intact in the thioacetamide-treated rats. The oxygen consumption associated with palmitoyl-coenzyme A and palmitoyl-L-carnitine oxidation by isolated liver mitochondria was increased by thioacetamide treatment on both a per-mitochondrial protein and a per-total liver basis. The carnitine palmitoyl-transferase I activity; the tissue levels of ketone bodies, carnitine and carnitine esters; and the beta-hydroxybutyrate/acetoacetate ratio were all higher in the livers of thioacetamide-treated animals than in control livers, whereas the hepatic malonyl-coenzyme A level was decreased by thioacetamide. These results indicate the increased diversion of cytosolic long-chain acyl-coenzyme As into the mitochondria for beta-oxidation rather than their esterification and use in lipogenesis. These intrahepatic metabolic changes induced by chronic thioacetamide administration may reflect the whole-body catabolic state and can be seen as adaptive for maintaining energy homeostasis under conditions of impaired glucose tolerance.

MeSH terms

  • Animals
  • Carnitine / metabolism
  • Carnitine O-Palmitoyltransferase / metabolism
  • Fatty Acids / metabolism*
  • Ketone Bodies / metabolism
  • Liver / drug effects
  • Liver / enzymology
  • Liver / metabolism*
  • Liver Cirrhosis, Experimental / chemically induced
  • Liver Cirrhosis, Experimental / enzymology
  • Liver Cirrhosis, Experimental / metabolism*
  • Male
  • Malonyl Coenzyme A / metabolism
  • Mitochondria, Liver / enzymology
  • Mitochondria, Liver / metabolism
  • Oxidation-Reduction
  • Oxygen / metabolism
  • Palmitoyl Coenzyme A / metabolism
  • Palmitoylcarnitine / metabolism
  • Rats
  • Rats, Inbred Strains
  • Thioacetamide / administration & dosage*
  • Thioacetamide / pharmacology
  • Time Factors


  • Fatty Acids
  • Ketone Bodies
  • Thioacetamide
  • Palmitoyl Coenzyme A
  • Palmitoylcarnitine
  • Malonyl Coenzyme A
  • Carnitine O-Palmitoyltransferase
  • Carnitine
  • Oxygen