Folic acid supplementation during the juvenile-pubertal period in rats modifies the phenotype and epigenotype induced by prenatal nutrition
Open accessAbstract
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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Reproduction in contemporary forager societies begins several years after adolescence.
“Reproduction in contemporary forager societies also begins several years after adolescence and post-adolescent individuals are often limited in their gathering and/or hunting skills (3–5).”
From Emerging Adulthood, a Pre-adult Life-History Stage (2020) · cites this paper as [3]
Post-adolescent individuals in contemporary forager societies are often limited in their gathering and/or hunting skills.
“Reproduction in contemporary forager societies also begins several years after adolescence and post-adolescent individuals are often limited in their gathering and/or hunting skills (3–5).”
From Emerging Adulthood, a Pre-adult Life-History Stage (2020) · cites this paper as [3]
In contrast to great apes, primiparous women of human forager populations are provisioned by mature adults, such as post-reproductive grandmothers, husbands several years older who have often passed through emerging adulthood, and other adults.
“In contrast to great apes, primiparous women of human forager populations are provisioned by mature adults, such as grandmothers, who are usually post-reproductive (77, 78); their husbands, who are typically several years older and have often passed through the emerging adulthood stage of their life history before marriage; and other adults (3, 79–81).”
From Emerging Adulthood, a Pre-adult Life-History Stage (2020) · cites this paper as [3]
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References 40 · Cited by 213
- Authors
- Burdge, G. C., Lillycrop, K. A., Phillips, E. S., Slater-Jefferies, J. L., Jackson, A. A., & Hanson, M. A.
- Affiliations
- University of Southampton (GB)
- Corresponding author
- Burdge, Graham C.
- ORCID
- Venue
- The Journal of Nutrition
- Publisher
- Elsevier BV
- Published
- 2009-06
- Volume
- 139
- Issue
- 6
- Pages
- 1054-1060
- ISSN
- 0022-3166 (ISSN-L)
- OpenAlex
- W2118177002
- Cited by
- 213
- References
- 40
- Citations by year
- 2025: 3 · 2024: 10 · 2023: 5 · 2022: 5 · 2021: 4 · 2020: 4 · 2019: 5 · 2018: 9 · 2017: 9 · 2016: 12 · 2015: 14 · 2014: 14 · 2013: 24 · 2012: 30
- FWCI
- 28.13
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of Nutrition (publishedVersion)
- PubMed (publishedVersion)
- ePrints Soton (University of Southampton) (submittedVersion)
- Funders
- British Heart Foundation (FS/05/064/19525)
- Topics
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
- Health Sciences › Medicine › Rheumatology › Folate and B Vitamins Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Keywords
- folic acid supplementation, prenatal protein restriction, maternal nutrition, epigenetic methylation, PPARα, glucocorticoid receptor, insulin receptor, high-fat diet, fasting plasma triglycerides, beta-hydroxybutyrate, hepatic lipid metabolism, developmental plasticity, offspring phenotype, rats
- MeSH terms
- Adipose Tissue, Aging, Animals, Diet, Dietary Fats, Fatty Acids, Nonesterified, Female, Folic Acid, Gene Expression Regulation, Lipase, Liver, Male, Phenotype, Pregnancy, Random Allocation, RNA, Messenger, Sexual Maturation, Rats, Wistar, Muscle, Skeletal, Gene Expression Profiling, Prenatal Nutritional Physiological Phenomena, Epigenesis, Genetic, Rats
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