COORDINATE INDUCTION OF ACYL-COA BINDING-PROTEIN, FATTY-ACID BINDING-PROTEIN AND PEROXISOMAL BETA-OXIDATION BY PEROXISOME PROLIFERATORS

Acyl-CoA binding protein (ACBP) and fatty acid binding protein (FABP) are important intracellular lipid binding proteins. The purpose of the present experiments was to test the hypothesis that peroxisome prolif erators induce ACBP in rat hepatocytes as has been shown previously fo r FABP. The effects of two structurally dissimilar peroxisome prolifer ators perfluorodecanoic acid (PFDA) and clofibric acid (CPIB) were exa mined in primary rat hepatocyte cultures in a chemically defined media . Both compounds alter lipid metabolism in primary rat hepatocytes in a similar fashion, although PFDA is more potent than CPIB at inducing peroxisomal beta-oxidation. In addition, PFDA and CPIB compete with lo ng-chain fatty acids for binding to FABP but do not compete with long- chain acyl-CoA esters for binding to ACBP. The concentration of ACBP a nd FABP was increased in peroxisome proliferator-treated hepatocytes r elative to vehicle controls within 48 h of treatment. Evidence is give n to support increases in ACBP and FABP mRNA being the cause of the in creased protein levels by peroxisome proliferators. In addition, the p eroxisome proliferators PFDA, perfluorooctanoic acid and ciprofibrate induced hepatic ACBP following in vivo administration to rats indicati ng that this phenomena is not exclusive to in vitro systems. Therefore , ACBP appears to be a member of the peroxisome proliferator loci, a g roup of lipid metabolizing proteins, including FABP, which are regulat ed by peroxisome proliferators such as fibric acids and perfluorinated fatty acids.