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.

Abstract

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.

• Authors: D J Shin, M M McGrane
• Journal: The Journal of nutrition (J Nutr) Vol. 127 Issue 7 Pg. 1274-8 (Jul 1997) ISSN: 0022-3166 [Print] United States
• PMID: 9202079 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• RNA, Messenger
• Vitamin A
• Tretinoin
• Bucladesine
• Phosphofructokinase-1
• Fructose-Bisphosphatase
• Phosphoenolpyruvate Carboxykinase (GTP)

Topics

• Animals
• Bucladesine (pharmacology)
• Food Deprivation (physiology)
• Fructose-Bisphosphatase (biosynthesis, genetics)
• Gene Expression Regulation, Enzymologic (drug effects)
• Gluconeogenesis (drug effects, genetics)
• Liver (chemistry, enzymology, metabolism)
• Mice
• Mice, Inbred C57BL
• Phosphoenolpyruvate Carboxykinase (GTP) (biosynthesis, genetics)
• Phosphofructokinase-1 (biosynthesis, genetics)
• Promoter Regions, Genetic (genetics)
• RNA, Messenger (analysis, metabolism)
• Tretinoin (pharmacology)
• Vitamin A (pharmacology)
• Vitamin A Deficiency (genetics, metabolism, physiopathology)