Increasing the folic acid content of maternal or post-weaning diets induces differential changes in phospheonolypyruvate carboxykinase mRNA expression and promoter methylation in rats
Increasing the folic acid content of maternal or post-weaning diets induces differential changes in phospheonolypyruvate carboxykinase mRNA expression and promoter methylation in rats
Environmental exposures throughout the life course, including nutrition, may induce phenotypic and epigenetic changes. There is limited information about how timing affects the nature of such effects induced by a specific nutritional exposure. We investigated the effect of increased exposure to folic acid before birth or during the juvenile–pubertal period in rats on the epigenetic regulation of glucose homeostasis. Rats were fed either a folic acid-adequate (AF; 1 mg/kg feed) or a folic acid-supplemented (FS; 5 mg/kg feed) diet from conception until delivery and then an AF diet during lactation. Juvenile rats were fed either the AF or the FS diet from weaning for 28 d and then an AF diet. Liver and blood were collected after a 12 h fast between postnatal days 84 and 90. Maternal FS diet increased plasma glucose concentration significantly (P < 0·05) in females, but not in males. Post-weaning FS diet decreased glucose concentration significantly in females, but increased glucose concentration in males. There were no effects of the FS diet on phosphoenolpyruvate carboxykinase (PEPCK) mRNA expression in males, while the pattern of expression was related to plasma glucose concentration in females. The FS diet induced specific changes in the methylation of individual CpG in females, but not in males, which were related to the time of exposure. Methylation of CpG ? 248 increased the binding of CCAAT-enhancer-binding protein ? to the PEPCK promoter. Together, these findings show that both the period during the life course and sex influence the effect of increased exposure to folic acid on the epigenetic regulation of PEPCK and glucose homeostasis.
epigenetic regulation, phosphoenolpyruvate carboxykinase, folic acid, rats
852-857
Hoile, Samuel P.
9d7e9816-600d-45bd-ade2-dc7798bba730
Lillycrop, Karen A.
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Grenfell, Leonie R.
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Hanson, Mark A.
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Burdge, Graham C.
09d60a07-8ca1-4351-9bf1-de6ffcfb2159
September 2012
Hoile, Samuel P.
9d7e9816-600d-45bd-ade2-dc7798bba730
Lillycrop, Karen A.
eeaaa78d-0c4d-4033-a178-60ce7345a2cc
Grenfell, Leonie R.
ea8a6901-506a-45df-8e86-fed7afedbcf7
Hanson, Mark A.
1952fad1-abc7-4284-a0bc-a7eb31f70a3f
Burdge, Graham C.
09d60a07-8ca1-4351-9bf1-de6ffcfb2159
Hoile, Samuel P., Lillycrop, Karen A., Grenfell, Leonie R., Hanson, Mark A. and Burdge, Graham C.
(2012)
Increasing the folic acid content of maternal or post-weaning diets induces differential changes in phospheonolypyruvate carboxykinase mRNA expression and promoter methylation in rats.
British Journal of Nutrition, 108 (5), .
(doi:10.1017/S0007114511006155).
(PMID:22136740)
Abstract
Environmental exposures throughout the life course, including nutrition, may induce phenotypic and epigenetic changes. There is limited information about how timing affects the nature of such effects induced by a specific nutritional exposure. We investigated the effect of increased exposure to folic acid before birth or during the juvenile–pubertal period in rats on the epigenetic regulation of glucose homeostasis. Rats were fed either a folic acid-adequate (AF; 1 mg/kg feed) or a folic acid-supplemented (FS; 5 mg/kg feed) diet from conception until delivery and then an AF diet during lactation. Juvenile rats were fed either the AF or the FS diet from weaning for 28 d and then an AF diet. Liver and blood were collected after a 12 h fast between postnatal days 84 and 90. Maternal FS diet increased plasma glucose concentration significantly (P < 0·05) in females, but not in males. Post-weaning FS diet decreased glucose concentration significantly in females, but increased glucose concentration in males. There were no effects of the FS diet on phosphoenolpyruvate carboxykinase (PEPCK) mRNA expression in males, while the pattern of expression was related to plasma glucose concentration in females. The FS diet induced specific changes in the methylation of individual CpG in females, but not in males, which were related to the time of exposure. Methylation of CpG ? 248 increased the binding of CCAAT-enhancer-binding protein ? to the PEPCK promoter. Together, these findings show that both the period during the life course and sex influence the effect of increased exposure to folic acid on the epigenetic regulation of PEPCK and glucose homeostasis.
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Accepted/In Press date: 5 December 2011
Published date: September 2012
Keywords:
epigenetic regulation, phosphoenolpyruvate carboxykinase, folic acid, rats
Organisations:
Human Development & Health, Centre for Biological Sciences
Identifiers
Local EPrints ID: 337118
URI: http://eprints.soton.ac.uk/id/eprint/337118
ISSN: 0007-1145
PURE UUID: 795c478f-679c-47e7-871e-cdf1f5f7a411
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Date deposited: 18 Apr 2012 13:25
Last modified: 15 Mar 2024 03:07
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Author:
Samuel P. Hoile
Author:
Leonie R. Grenfell
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