title: Simultaneous stimulation of fatty acid synthesis and oxidation in rat hepatocytes by vanadate.
abstract: When added to the hepatocyte incubation medium, vanadate increased the rate of fatty acid synthesis de novo as well as the activity of acetyl-CoA carboxylase, whereas it had no effect on the activity of fatty acid synthase. On the other hand, and despite elevating the intracellular levels of malonyl-CoA, vanadate diverted exogenous fatty acids into the oxidation pathway at the expense of the esterification route. This was concomitant to an increase in carnitine palmitoyltransferase I activity. All these effects were not significantly different between periportal and perivenous hepatocytes and were also evident in cells incubated in Ca2(+)-free medium. Nevertheless, Ca2+ ions enhanced carnitine palmitoyltransferase I activity in isolated liver mitochondria. In addition, the effects of vanadate on acetyl-CoA carboxylase and carnitine palmitoyltransferase I were only evident in a permeabilized-cell assay, disappearing upon cell disruption and isolation of the corresponding cell subfraction for enzyme assay. Results show that vanadate exerts specific insulin-like and non-insulin-like effects on hepatic fatty acid metabolism, and suggest that the intracellular concentration of malonyl-CoA is not the only factor responsible for the regulation of the fatty-acid-oxidative process in the liver.
authors.affiliation: Department of Biochemistry and Molecular Biology I, Faculty of Chemistry, Complutense University, Madrid, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Guzmán
authors.forename: J
authors.initials: J
authors.lastname: Castro
mesh_terms: D000103:Acetyl-CoA Carboxylase / Q000378:metabolism; D000818:Animals; D002122:Calcium Chloride / Q000494:pharmacology; D002334:Carnitine O-Palmitoyltransferase / Q000378:metabolism; D002478:Cells, Cultured; D005227:Fatty Acids / Q000096:biosynthesis / Q000378:metabolism*; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010084:Oxidation-Reduction; D051381:Rats; D011919:Rats, Inbred Strains; D014638:Vanadates / Q000494:pharmacology*
chemical_list: D005227:Fatty Acids; D014638:Vanadates; D002334:Carnitine O-Palmitoyltransferase; D000103:Acetyl-CoA Carboxylase; D002122:Calcium Chloride