Ntambi J M
Department of Biochemistry and Molecular Biology, Georgetown University School of Medicine, Washington, D.C. 20007.
J Biol Chem. 1992 May 25;267(15):10925-30.
Expression of the murine liver stearoyl-CoA desaturase gene (SCD1) is induced upon feeding fasted mice a fat-free, high carbohydrate diet (Ntambi, J. M., Buhrow, S. A., Kaestner, K. H., Christy, R. J., Sibley, E., Kelly, T. J., and Lane, M.D. (1988) J. Biol. Chem. 263, 17291-17300). In the present study, SCD1-specific RNA riboprobes and cDNA probes were used to study the mechanism for the induction of SCD1 mRNA. Based on the time course of induction, the SCD1 mRNA increased from 2-fold within 6 h to 45-fold within 36 h. Nuclear run-on transcription studies showed that the accumulation of SCD1 mRNA after refeeding starved mice a fat-free, high carbohydrate diet was a consequence of the transcriptional activation of the SCD1 gene. The SCD1 mRNA level decreased rapidly (t1/2 = approximately 4 h) within 24 h when mice fed the fat-free, high carbohydrate diet were switched to a regular chow diet. Furthermore, when the fat-free diet was supplemented with triacylglycerides containing polyunsaturated fatty acids, the transcription of the SCD1 gene and the induction of the SCD1 mRNA were significantly blunted. Triacylglycerides containing saturated and monounsaturated fatty acids were without dramatic effects. In contrast, synthesis of liver albumin mRNA was little affected by any of these dietary variations, indicating that the observed changes in the transcription of the SCD1 gene and mRNA levels were specific. These data demonstrate that both dietary carbohydrates and polyunsaturated fatty acids or their metabolites directly or indirectly regulate the expression of the SCD1 gene in mouse liver.
给禁食的小鼠喂食无脂肪、高碳水化合物饮食后,小鼠肝脏硬脂酰辅酶A去饱和酶基因(SCD1)的表达会被诱导(Ntambi, J. M., Buhrow, S. A., Kaestner, K. H., Christy, R. J., Sibley, E., Kelly, T. J., and Lane, M.D. (1988) J. Biol. Chem. 263, 17291 - 17300)。在本研究中,使用SCD1特异性RNA核糖探针和cDNA探针来研究SCD1 mRNA诱导的机制。根据诱导的时间进程,SCD1 mRNA在6小时内从2倍增加到36小时内的45倍。核转录活性分析表明,给饥饿小鼠重新喂食无脂肪、高碳水化合物饮食后SCD1 mRNA的积累是SCD1基因转录激活的结果。当喂食无脂肪、高碳水化合物饮食的小鼠改为常规饲料饮食时,SCD1 mRNA水平在24小时内迅速下降(半衰期约为4小时)。此外,当无脂肪饮食中添加含有多不饱和脂肪酸的甘油三酯时,SCD1基因的转录和SCD1 mRNA的诱导明显受到抑制。含有饱和脂肪酸和单不饱和脂肪酸的甘油三酯没有显著影响。相比之下,肝脏白蛋白mRNA的合成几乎不受这些饮食变化的影响,这表明观察到的SCD1基因转录和mRNA水平的变化是特异性的。这些数据表明,饮食中的碳水化合物和多不饱和脂肪酸或其代谢产物直接或间接调节小鼠肝脏中SCD1基因的表达。