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

• Published in: The Journal of nutrition Vol. 127; no. 7; pp. 1274 - 1278
• Main Authors: Shin, D.J. (The University of Connecticut, Storrs, CT.), McGrane, M.M
• Format: Journal Article
• Language: English
• Published: Bethesda, MD American Society for Nutritional Sciences 01.07.1997; American Institute of Nutrition
• Subjects: ANIMAL MODELS; Animals; ARN MENSAJERO; ARN MESSAGER; Biological and medical sciences; Bucladesine - pharmacology; CARENCE EN VITAMINE; Cellular biology; COMPLEMENT ALIMENTAIRE; DEFICIENCIA DE VITAMINAS; Enzymes. Coenzymes. Vitamins. Pigments; ESTERASAS; ESTERASE; ESTERASES; EXPRESION GENICA; EXPRESSION DES GENES; FOIE; Food Deprivation - physiology; FOSFENOLPIRUVATO CARBOXILASA; FRUCTOSE-BISPHOSPHATASE; Fructose-Bisphosphatase - biosynthesis; Fructose-Bisphosphatase - genetics; Fundamental and applied biological sciences. Psychology; GENE EXPRESSION; Gene Expression Regulation, Enzymologic - drug effects; Genes; GLUCONEOGENESE; GLUCONEOGENESIS; Gluconeogenesis - drug effects; Gluconeogenesis - genetics; HIGADO; INANICION; INANITION; LIVER; Liver - chemistry; Liver - enzymology; Liver - metabolism; MESSENGER RNA; Metabolisms and neurohumoral controls; MICE; Mice, Inbred C57BL; MODELE ANIMAL; MODELOS ANIMALES; Phosphoenolpyruvate Carboxykinase (GTP) - biosynthesis; Phosphoenolpyruvate Carboxykinase (GTP) - genetics; PHOSPHOENOLPYRUVATE CARBOXYLASE; PHOSPHOFRUCTOKINASE; Phosphofructokinase-1 - biosynthesis; Phosphofructokinase-1 - genetics; Promoter Regions, Genetic - genetics; RATON; RETINOIC ACID; RETINOL; RNA, Messenger - analysis; RNA, Messenger - metabolism; Rodents; SOURIS; STARVATION; SUPLEMENTOS; SUPPLEMENTS; TRANSFERASAS; TRANSFERASE; TRANSFERASES; Tretinoin - pharmacology; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Vitamin A; Vitamin A - pharmacology; Vitamin A Deficiency - genetics; Vitamin A Deficiency - metabolism; Vitamin A Deficiency - physiopathology; VITAMIN DEFICIENCIES; VITAMINAS; VITAMINE; VITAMINS; Fructose-bisphosphatase; Deficient diet; Enzyme; Transferases; Liver; Rodentia; Vitamin; Phosphoric monoester hydrolases; Esterases; Lyases; Metabolism; Gene expression; Retinol; Carbon-carbon lyases; Vertebrata; Regulation(control); Mammalia; Mouse; Carboxy-lyases; Hydrolases; 6-Phosphofructo-2-kinase; Phosphoenolpyruvate carboxykinase (GTP); Gluconeogenesis
• ISSN: 0022-3166; 1541-6100
• 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 c...