Shin D J, McGrane M M
Department of Nutritional Sciences, University of Connecticut, Storrs, CT 06269, USA.
J Nutr. 1997 Jul;127(7):1274-8. doi: 10.1093/jn/127.7.1274.
We examined the effects of vitamin A deficiency and all-trans retinoic acid (RA) supplementation on regulation of three important genes in hepatic gluconeogenesis: the genes for phosphoenolpyruvate carboxykinase (PEPCK), fructose-1,6-bisphosphatase (Fru-1,6-P2ase) and 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (6-PF-2-K/Fru-2,6-P2ase). Mice were made vitamin A deficient in the second generation by initiating a vitamin A-deficient diet on d 10 of gestation. At 7 wk of age, vitamin A-deficient mice were treated with all-trans RA or vehicle alone and killed for RNA analysis. In liver, vitamin A deficiency resulted in PEPCK mRNA levels that were 74% lower and 6-PF-2-K/Fru-2,6-P2ase mRNA levels that were 42% lower than the respective mRNA measured in control mice. The Fru-1,6-P2ase mRNA abundance was not affected by vitamin A deficiency. The decrease in hepatic PEPCK and 6-PF-2-K/Fru-2,6-P2ase mRNA levels was reversed by treatment with all-trans RA within 3 h of administration. In mice fed the control diet, food deprivation for 15 h resulted in PEPCK mRNA levels that were 3.5-fold higher, Fru-1,6-P2ase mRNA levels that were 2-fold higher, and 6-PF-2-K/Fru-2,6-P2ase mRNA levels that were 3.4-fold higher than in fed mice. Vitamin A-deficient mice did not respond to food deprivation with induced PEPCK mRNA levels, whereas 6-PF-2-K/Fru-2,6-P2ase and Fru-1,6-P2ase mRNA levels were induced. The pattern of 6-PF-2-K/Fru-2,6-P2ase mRNA abundance with vitamin A deficiency and food deprivation was complex and different from that for either PEPCK or Fru-1,6-P2ase transcripts. The cAMP-responsiveness of the PEPCK gene in vitamin A-deficient mice was tested. Vitamin A deficiency caused a significant reduction in cAMP stimulation of PEPCK mRNA levels in liver. These results in the whole animal indicate that vitamin A regulation of the hepatic PEPCK gene is physiologically important; without adequate vitamin A nutriture, stimulation of the PEPCK gene by food deprivation or cAMP treatment is inhibited in the liver.
我们研究了维生素A缺乏和补充全反式视黄酸（RA）对肝脏糖异生过程中三个重要基因调控的影响，这三个基因分别是磷酸烯醇式丙酮酸羧激酶（PEPCK）基因、果糖-1,6-二磷酸酶（Fru-1,6-P2ase）基因和6-磷酸果糖-2-激酶/果糖-2,6-二磷酸酶（6-PF-2-K/Fru-2,6-P2ase）基因。在妊娠第10天开始给予维生素A缺乏饮食，使第二代小鼠维生素A缺乏。7周龄时，对维生素A缺乏的小鼠用全反式视黄酸或单独用赋形剂处理，然后处死进行RNA分析。在肝脏中，维生素A缺乏导致PEPCK mRNA水平比对照小鼠中测得的相应mRNA低74%，6-PF-2-K/Fru-2,6-P2ase mRNA水平低42%。Fru-1,6-P2ase mRNA丰度不受维生素A缺乏的影响。给予全反式视黄酸处理3小时内，肝脏中PEPCK和6-PF-2-K/Fru-2,6-P2ase mRNA水平的降低得以逆转。在喂食对照饮食的小鼠中，禁食15小时导致PEPCK mRNA水平比进食小鼠高3.5倍，Fru-1,6-P2ase mRNA水平高2倍，6-PF-2-K/Fru-2,6-P2ase mRNA水平高3.4倍。维生素A缺乏的小鼠对禁食诱导的PEPCK mRNA水平无反应，而6-PF-2-K/Fru-2,6-P2ase和Fru-1,6-P2ase mRNA水平受到诱导。维生素A缺乏和禁食时6-PF-2-K/Fru-2,6-P2ase mRNA丰度的模式复杂，与PEPCK或Fru-1,6-P2ase转录本的模式不同。对维生素A缺乏小鼠中PEPCK基因的cAMP反应性进行了测试。维生素A缺乏导致肝脏中cAMP对PEPCK mRNA水平的刺激显著降低。在整体动物中的这些结果表明，维生素A对肝脏PEPCK基因的调控在生理上很重要；在没有足够维生素A营养的情况下，肝脏中禁食或cAMP处理对PEPCK基因的刺激受到抑制。
