Folic acid supplementation during the juvenile-pubertal period in rats modifies the phenotype and epigenotype induced by prenatal nutrition
Folic acid supplementation during the juvenile-pubertal period in rats modifies the phenotype and epigenotype induced by prenatal nutrition
Prenatal nutritional constraint is associated with increased risk of metabolic dysregulation in adulthood contingent on adult diet. In rats, folic acid supplementation of a protein-restricted (PR) diet during pregnancy prevents altered phenotype and epigenotype in the offspring induced by the PR diet. We hypothesized that increasing folic acid intake during the juvenile-pubertal (JP) period would reverse the effects of a maternal PR diet on the offspring. Rats were fed a control (C) or PR diet during pregnancy and AIN93G during lactation. Offspring were weaned on d 28 onto diets containing 1 mg [adequate folate (AF)] or 5 mg [folic acid-supplemented (FS)] folic acid/kg feed. After 28 d, all offspring were fed a high-fat (18% wt:wt) diet and killed on d 84. As expected, offspring of PR dams fed the AF diet had increased fasting plasma triglyceride (TAG) and beta-hydroxybutyrate (betaHB) concentrations. The FS diet induced increased weight gain, a lower plasma betaHB concentration, and increased hepatic and plasma TAG concentration compared with AF offspring irrespective of maternal diet. PPARalpha and glucocorticoid receptor promoter methylation increased in liver and insulin receptor promoter methylation decreased in liver and adipose tissue in FS compared with AF offspring, with reciprocal changes in mRNA expression irrespective of maternal diet. These findings show that increased folic acid intake during the JP period did not simply reverse the phenotype induced by the maternal diet. This may represent a period of plasticity when specific nutrient intakes may alter the phenotype of the offspring through epigenetic changes in specific genes.
folic acid, phenotype, epigenotype
1054-1060
Burdge, Graham C.
09d60a07-8ca1-4351-9bf1-de6ffcfb2159
Lillycrop, Karen A.
eeaaa78d-0c4d-4033-a178-60ce7345a2cc
Phillips, Emma S.
36b8c608-f279-4239-87c0-32df46ced0c7
Slater-Jefferies, Joanne L.
e46c711a-9d4c-436a-b853-828df69bb4d7
Jackson, Alan A.
c9a12d7c-b4d6-4c92-820e-890a688379ef
Hanson, Mark A.
1952fad1-abc7-4284-a0bc-a7eb31f70a3f
June 2009
Burdge, Graham C.
09d60a07-8ca1-4351-9bf1-de6ffcfb2159
Lillycrop, Karen A.
eeaaa78d-0c4d-4033-a178-60ce7345a2cc
Phillips, Emma S.
36b8c608-f279-4239-87c0-32df46ced0c7
Slater-Jefferies, Joanne L.
e46c711a-9d4c-436a-b853-828df69bb4d7
Jackson, Alan A.
c9a12d7c-b4d6-4c92-820e-890a688379ef
Hanson, Mark A.
1952fad1-abc7-4284-a0bc-a7eb31f70a3f
Burdge, Graham C., Lillycrop, Karen A., Phillips, Emma S., Slater-Jefferies, Joanne L., Jackson, Alan A. and Hanson, Mark A.
(2009)
Folic acid supplementation during the juvenile-pubertal period in rats modifies the phenotype and epigenotype induced by prenatal nutrition.
Journal of Nutrition, 139 (6), .
(doi:10.3945/jn.109.104653).
Abstract
Prenatal nutritional constraint is associated with increased risk of metabolic dysregulation in adulthood contingent on adult diet. In rats, folic acid supplementation of a protein-restricted (PR) diet during pregnancy prevents altered phenotype and epigenotype in the offspring induced by the PR diet. We hypothesized that increasing folic acid intake during the juvenile-pubertal (JP) period would reverse the effects of a maternal PR diet on the offspring. Rats were fed a control (C) or PR diet during pregnancy and AIN93G during lactation. Offspring were weaned on d 28 onto diets containing 1 mg [adequate folate (AF)] or 5 mg [folic acid-supplemented (FS)] folic acid/kg feed. After 28 d, all offspring were fed a high-fat (18% wt:wt) diet and killed on d 84. As expected, offspring of PR dams fed the AF diet had increased fasting plasma triglyceride (TAG) and beta-hydroxybutyrate (betaHB) concentrations. The FS diet induced increased weight gain, a lower plasma betaHB concentration, and increased hepatic and plasma TAG concentration compared with AF offspring irrespective of maternal diet. PPARalpha and glucocorticoid receptor promoter methylation increased in liver and insulin receptor promoter methylation decreased in liver and adipose tissue in FS compared with AF offspring, with reciprocal changes in mRNA expression irrespective of maternal diet. These findings show that increased folic acid intake during the JP period did not simply reverse the phenotype induced by the maternal diet. This may represent a period of plasticity when specific nutrient intakes may alter the phenotype of the offspring through epigenetic changes in specific genes.
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Published date: June 2009
Keywords:
folic acid, phenotype, epigenotype
Organisations:
Dev Origins of Health & Disease, Biological Sciences
Identifiers
Local EPrints ID: 69044
URI: http://eprints.soton.ac.uk/id/eprint/69044
ISSN: 0022-3166
PURE UUID: 076405cf-edb4-4f0d-8c07-03faf98b928e
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Date deposited: 19 Oct 2009
Last modified: 14 Mar 2024 02:51
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Author:
Emma S. Phillips
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