Effect of sucrose diet on apolipoprotein biosynthesis in rat liver. Increase in apolipoprotein E gene transcription

A sucrose-rich diet stimulates the biosynthesis of very low density lipoproteins in rat liver. This diet also increases the triglyceride content of hepatic very low density lipoproteins and changes their apolipoprotein composition. To study the changes of hepatic apolipoprotein biogenesis in response to such a diet, we measured secretory rates of apolipoproteins A-I, B, and E in cultured rat hepatocytes. In cultures from rats fed the sucrose-rich diet the production of apolipoprotein E was increased 2-fold as compared to controls, whereas the production of apolipoproteins A-I and B was unchanged. The enhanced production of apolipoprotein E could be accounted for by a 2-fold increase in hepatic apolipoprotein E mRNA, as measured by slot blot hybridization. To characterize the mechanisms leading to the increase of liver apolipoprotein E mRNA levels we measured the transcriptional activity of the apolipoprotein E gene in a cell-free transcription system using isolated liver cell nuclei. Transcriptional activity of the apolipoprotein E gene was 7% that of albumin gene transcription in control animals. In rats fed a sucrose-rich diet the transcription rate of the apolipoprotein E gene increased to 140±11% of controls. There was no change in albumin gene transcription. Thus, a sucrose-rich diet enhances apolipoprotein E biosynthesis in rat liver, at least in part, by stimulating transcription of the apolipoprotein E gene.