GENE-EXPRESSION OF ENZYMES REGULATING KETOGENESIS AND FATTY-ACID METABOLISM IN REGENERATING RAT-LIVER

Levels of mRNA for mitochondrial 3-hydroxy-3-methylglutaryl-CoA (HMG-C oA) synthase, carnitine palmitoyltransferase I (CPT I) and carnitine p almitoyltransferase II (CPT II), fatty acid synthase (FAS) and actin w ere analysed during liver regeneration. mRNA levels for mitochondrial HMG-CoA synthase decreased rapidly, reaching a minimum 12 h after part ial hepatectomy and returning to normal at 24-36 h. In contrast, CPT I , CPT II and FAS mRNAs increased throughout the period examined. Expre ssion of actin increased significantly during regeneration. Levels of mRNA for mitochondrial HMG-CoA synthase also decreased as a result of surgical stress, although the effect of hepatectomy was much greater. We determined the levels of mitochondrial HMG-CoA synthase using speci fic antibodies. The amount of protein rapidly decreased, although less markedly than the corresponding mRNA levels. These results show that the decrease described in ketogenesis in partially hepatectomized rats correlated with the decrease in the expression of mitochondrial HMG-C oA synthase, suggesting that this enzyme may also be a control point i n ketogenesis in the regenerating liver, as it is in normal and diabet ic rats.