THE ROLE OF CITRATE IN THE REGULATION OF HEPATIC FATTY-ACID SYNTHESISBY INSULIN AND GLUCAGON

Incubation of intact rat hepatocytes with insulin and glucagon resulte d in increased and decreased rates of de novo fatty acid biosynthesis, respectively. These changes were paralleled by corresponding alterati ons in the activity of acetyl-CoA carboxylase, an important regulatory enzyme of this pathway. The hormonal conditions imposed on the hepato cytes did not change the cellular or the cytosolic level of citrate. I ncubation of hepatocytes with octanoate showed a parallel increase in the rate of fatty acid synthesis and acetyl-CoA carboxylase with a con comitant elevation of the cellular citrate level. The increase in whol e-cell citrate was mainly due to a marked increase in the level of cyt osolic citrate. Collectively, our data indicate that insulin and gluca gon-determined changes in acetyl-CoA carboxylase are not mediated by c hanges in cytosolic citrate levels.