The Journal of Nutrition Vol. 127 No. 7 July 1997, pp. 1274-1278
Copyright ©1997 by the American Society for Nutritional Sciences

Vitamin A Regulates Genes Involved in Hepatic Gluconeogenesis in Mice: Phosphoenolpyruvate Carboxykinase, Fructose-1,6-bisphosphatase and 6-Phosphofructo-2-kinase/Fructose-2,6-bisphosphatase

Manuscript received 3 July 1996. Initial reviews completed 12 August 1996. Revision accepted 4 March 1997.

Departments of Nutritional Sciences and Molecular and Cell Biology, The University of Connecticut, Storrs, CT 06269

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.

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