title: Changes of hepatic fatty acid metabolism produced by chronic thioacetamide administration in rats.
abstract: 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.
authors.affiliation: Department of Emergency and Critical Care Medicine, Kansai Medical University, Osaka, Japan.
authors.forename: F
authors.initials: F
authors.lastname: Nozu
authors.forename: N
authors.initials: N
authors.lastname: Takeyama
authors.forename: T
authors.initials: T
authors.lastname: Tanaka
mesh_terms: D000818:Animals; D002331:Carnitine / Q000378:metabolism; D002334:Carnitine O-Palmitoyltransferase / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism*; D007657:Ketone Bodies / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D008316:Malonyl Coenzyme A / Q000378:metabolism; D008930:Mitochondria, Liver / Q000201:enzymology / Q000378:metabolism; D010084:Oxidation-Reduction; D010100:Oxygen / Q000378:metabolism; D010171:Palmitoyl Coenzyme A / Q000378:metabolism; D010172:Palmitoylcarnitine / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013853:Thioacetamide / Q000008:administration & dosage* / Q000494:pharmacology; D013997:Time Factors
chemical_list: D005227:Fatty Acids; D007657:Ketone Bodies; D013853:Thioacetamide; D010171:Palmitoyl Coenzyme A; D010172:Palmitoylcarnitine; D008316:Malonyl Coenzyme A; D002334:Carnitine O-Palmitoyltransferase; D002331:Carnitine; D010100:Oxygen