The Role of Citrate in the Regulation of Hepatic Fatty Acid Synthesis by Insulin and Glucagon

Abstract

Incubation of intact rat hepatocytes with insulin and glucagon resulted in increased and decreased rates of de novo fatty acid biosynthesis, respectively. These changes were paralleled by corresponding alterations in the activity of acetyl-CoA carboxylase, an important regulatory enzyme of this pathway. The hormonal conditions imposed on the hepatocytes did not change the cellular or the cytosolic level of citrate. Incubation of hepatocytes with octanoate showed a parallel increase in the rate of fatty acid synthesis and acetyl-CoA carboxylase with a concomitant elevation of the cellular citrate level. The increase in whole-cell citrate was mainly due to a marked increase in the level of cytosolic citrate. Collectively, our data indicate that insulin and glucagon-determined changes in acetyl-CoA carboxylase are not mediated by changes in cytosolic citrate levels.