Strobl W, Gorder N L, Fienup G A, Lin-Lee Y C, Gotto A M, Patsch W
Department of Medicine, Baylor College of Medicine, Houston, Texas 77030.
J Biol Chem. 1989 Jan 15;264(2):1190-4.
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.
富含蔗糖的饮食会刺激大鼠肝脏中极低密度脂蛋白的生物合成。这种饮食还会增加肝脏极低密度脂蛋白的甘油三酯含量，并改变其载脂蛋白组成。为了研究肝脏载脂蛋白生物合成在这种饮食作用下的变化，我们测定了培养的大鼠肝细胞中载脂蛋白A-I、B和E的分泌率。在来自喂食富含蔗糖饮食大鼠的培养物中，与对照组相比，载脂蛋白E的产量增加了2倍，而载脂蛋白A-I和B的产量没有变化。通过狭缝印迹杂交测定，肝脏载脂蛋白E mRNA增加了2倍，这可以解释载脂蛋白E产量的增加。为了表征导致肝脏载脂蛋白E mRNA水平升高的机制，我们使用分离的肝细胞核在无细胞转录系统中测量了载脂蛋白E基因的转录活性。在对照动物中，载脂蛋白E基因的转录活性是白蛋白基因转录活性的7%。在喂食富含蔗糖饮食的大鼠中，载脂蛋白E基因的转录率增加到对照组的140±11%。白蛋白基因转录没有变化。因此，富含蔗糖的饮食至少部分通过刺激载脂蛋白E基因的转录来增强大鼠肝脏中载脂蛋白E的生物合成。
