| Epigenetic changes in fetal hypothalamic energy regulating pathways are associated with maternal undernutrition and twinning. | |
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MedLine Citation:
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PMID: 22223754 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Undernutrition during pregnancy is implicated in the programming of offspring for the development of obesity and diabetes. We hypothesized that maternal programming causes epigenetic changes in fetal hypothalamic pathways regulating metabolism. This study used sheep to examine the effect of moderate maternal undernutrition (60 d before to 30 d after mating) and twinning to investigate changes in the key metabolic regulators proopiomelanocortin (POMC) and the glucocorticoid receptor (GR) in fetal hypothalami. Methylation of the fetal hypothalamic POMC promoter was reduced in underfed singleton, fed twin, and underfed twin groups (60, 73, and 63 decrease, respectively). This was associated with reduced DNA methyltransferase activity and altered histone methylation and acetylation. Methylation of the hypothalamic GR promoter was decreased in both twin groups and in maternally underfed singleton fetuses (52, 65, and 55% decrease, respectively). This correlated with changes in histone methylation and acetylation and increased GR mRNA expression in the maternally underfed singleton group. Alterations in GR were hypothalamic specific, with no changes in hippocampi. Unaltered levels of OCT4 promoter methylation indicated gene-specific effects. In conclusion, twinning and periconceptional undernutrition are associated with epigenetic changes in fetal hypothalamic POMC and GR genes, potentially resulting in altered energy balance regulation in the offspring.-Begum, G., Stevens, A., Smith, E. B., Connor, K., Challis, J. R. G., Bloomfield, F., White, A. Epigenetic changes in fetal hypothalamic energy regulating pathways are associated with maternal undernutrition and twinning. |
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Authors:
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Ghazala Begum; Adam Stevens; Emma Bolton Smith; Kristin Connor; John R G Challis; Frank Bloomfield; Anne White |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-1-5 |
Journal Detail:
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Title: The FASEB journal : official publication of the Federation of American Societies for Experimental Biology Volume: - ISSN: 1530-6860 ISO Abbreviation: - Publication Date: 2012 Jan |
Date Detail:
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Created Date: 2012-1-6 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8804484 Medline TA: FASEB J Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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*Faculty of Life Sciences and. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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