Zhang Yanqiao, Hillgartner F Bradley
Department of Biochemistry and Molecular Pharmacology, School of Medicine, West Virginia University, Morgantown, WV 26506, USA.
J Nutr. 2004 Sep;134(9):2205-10. doi: 10.1093/jn/134.9.2205.
In mammalian liver, the mature form of sterol regulatory element-binding protein-1c (SREBP-1c) is an important activator of a wide array of genes involved in triacylglycerol biosynthesis. Starvation and feeding a high-carbohydrate, low-fat diet modulate the concentration of mature SREBP-1c primarily by a pretranslational mechanism. It is not known whether alterations in nutritional status regulate the concentration of SREBPs in nonmammalian species. In this study, we found that in previously starved chicks, feeding a high-carbohydrate, low-fat diet stimulated a robust increase (14-fold at 5 h of feeding) in the concentration of mature SREBP-1 in liver. Feeding a high-carbohydrate, low-fat diet also increased the concentration of precursor SREBP-1 and SREBP-1 messenger RNA in chick liver; however, the magnitude of this effect was substantially lower than that observed for mature SREBP-1. DNA binding experiments demonstrated that 3 protein complexes containing SREBP bound the acetyl-CoA carboxylase-alpha (ACCalpha) sterol regulatory element (SRE) in chick liver and that the binding activity of 2 of these complexes was increased by consumption of a high-carbohydrate, low-fat diet. Additional analyses showed that feeding a high-carbohydrate, low-fat diet had no effect on the concentration of mature SREBP-2 and the binding of SREBP-2 to the ACCalpha SRE in chick liver. These results indicate that alterations in the concentration of mature SREBP-1 play a role in mediating the effects of starvation and feeding a high-carbohydrate, low-fat diet on ACCalpha transcription in chick liver and that diet-induced changes in mature SREBP-1 concentration in chick liver are mediated primarily by a posttranslational mechanism.
在哺乳动物肝脏中,固醇调节元件结合蛋白1c(SREBP-1c)的成熟形式是参与三酰甘油生物合成的众多基因的重要激活因子。饥饿以及喂食高碳水化合物、低脂饮食主要通过翻译前机制调节成熟SREBP-1c的浓度。目前尚不清楚营养状况的改变是否会调节非哺乳动物物种中SREBPs的浓度。在本研究中,我们发现,在先前饥饿的雏鸡中,喂食高碳水化合物、低脂饮食会刺激肝脏中成熟SREBP-1的浓度大幅增加(喂食5小时后增加14倍)。喂食高碳水化合物、低脂饮食还会增加雏鸡肝脏中前体SREBP-1和SREBP-1信使核糖核酸的浓度;然而,这种效应的幅度远低于成熟SREBP-1所观察到的幅度。DNA结合实验表明,含有SREBP的3种蛋白质复合物与雏鸡肝脏中的乙酰辅酶A羧化酶α(ACCalpha)固醇调节元件(SRE)结合,并且其中2种复合物的结合活性因食用高碳水化合物、低脂饮食而增加。进一步分析表明,喂食高碳水化合物、低脂饮食对雏鸡肝脏中成熟SREBP-2的浓度以及SREBP-2与ACCalpha SRE的结合没有影响。这些结果表明,成熟SREBP-1浓度的改变在介导饥饿和喂食高碳水化合物、低脂饮食对雏鸡肝脏中ACCalpha转录的影响中起作用,并且饮食诱导的雏鸡肝脏中成熟SREBP-1浓度的变化主要由翻译后机制介导。