title: Induction of hepatic acyl-CoA-binding protein and liver fatty acid-binding protein by perfluorodecanoic acid in rats. Lack of correlation with hepatic long-chain acyl-CoA levels.
abstract: Liver fatty acid-binding protein (L-FABP) and acyl-CoA-binding protein (ACBP) are involved in the intracellular trafficking and compartmentalization of fatty acids and fatty acyl-CoA esters, respectively, in the liver. Both proteins are induced in rat liver by the potent peroxisome proliferator perfluorodecanoic acid (PFDA). While it is believed that the peroxisome proliferator-activated receptor may mediate the responses to peroxisome proliferators by inducing responsive genes, the ligand(s) of this receptor remains unknown. We hypothesized that induction of L-FABP and ACBP in rat liver by PFDA is secondary to accumulation of long-chain acyl-CoA esters. However, neither dose-response nor time-course effects of PFDA on hepatic long-chain acyl-CoA, L-FABP, or ACBP concentrations confirmed this hypothesis. In a dose-response study, PFDA increased hepatic long-chain acyl-CoA concentrations (7 days after treatment) over the dose range of 20-50 mg/kg, whereas it increased ACBP and L-FABP over the wider dose range of 20-65 mg/kg. In the time-course study, PFDA treatment (50 mg/kg) elevated long-chain acyl-CoA esters in the liver beginning on day 3 post-treatment, yet hepatic L-FABP concentrations were increased earlier beginning on day 2 and ACBP was not induced until day 7. To determine if this dissociation of increases in hepatic long-chain acyl-CoA concentrations from increases in hepatic L-FABP and ACBP concentrations could be demonstrated under other conditions, control rats fasted for 24-48 hr were used. Fasting increased hepatic long-chain acyl-CoA levels to a greater extent than PFDA treatment, yet neither L-FABP nor ACBP was induced. We conclude that elevated concentrations of hepatic long-chain acyl-CoAs in PFDA-treated rats are not a major contributor to the induction of L-FABP or ACBP by peroxisome proliferators. A more plausible mechanism is that PFDA induces L-FABP and ACBP by activating the peroxisome proliferator receptor directly rather than indirectly through long-chain acyl-CoA esters.
authors.affiliation: School of Pharmacy, University of Wisconsin, Madison 53706.
authors.forename: P F
authors.initials: PF
authors.lastname: Sterchele
authors.forename: J P
authors.initials: JP
authors.lastname: Vanden Heuvel
authors.forename: J W
authors.initials: JW
authors.lastname: Davis
authors.forename: E
authors.initials: E
authors.lastname: Shrago
authors.forename: J
authors.initials: J
authors.lastname: Knudsen
authors.forename: R E
authors.initials: RE
authors.lastname: Peterson
mesh_terms: D000214:Acyl Coenzyme A / Q000378:metabolism*; D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000235:genetics; D003066:Coenzyme A Ligases / Q000235:genetics / Q000378:metabolism; D017931:DNA Primers; D003652:Decanoic Acids / Q000494:pharmacology*; D026261:Diazepam Binding Inhibitor; D004305:Dose-Response Relationship, Drug; D004952:Esters; D005215:Fasting; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D005227:Fatty Acids / Q000378:metabolism*; D005466:Fluorocarbons / Q000494:pharmacology*; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D000098859:Long-Chain-Fatty-Acid-CoA Ligase
chemical_list: D000214:Acyl Coenzyme A; D002352:Carrier Proteins; D017931:DNA Primers; D003652:Decanoic Acids; D026261:Diazepam Binding Inhibitor; D004952:Esters; C493320:Fabp1 protein, mouse; C493321:Fabp1 protein, rat; C490174:Fabp7 protein, rat; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D005227:Fatty Acids; D005466:Fluorocarbons; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; C036567:perfluorodecanoic acid; D003066:Coenzyme A Ligases; C090799:FAA2 protein, S cerevisiae; D000098859:Long-Chain-Fatty-Acid-CoA Ligase