Offspring of mothers fed a high fat diet display hepatic cell cycle inhibition and associated changes in gene expression and DNA methylation.

Show simple item record Dudley, KJ en Sloboda, Deborah en Connor, KL en Beltrand, J en Vickers, Mark en
dc.coverage.spatial United States en 2012-03-27T00:59:40Z en 2011 en
dc.identifier.citation PLoS One 6(7):e21662 2011 en
dc.identifier.uri en
dc.description.abstract The association between an adverse early life environment and increased susceptibility to later-life metabolic disorders such as obesity, type 2 diabetes and cardiovascular disease is described by the developmental origins of health and disease hypothesis. Employing a rat model of maternal high fat (MHF) nutrition, we recently reported that offspring born to MHF mothers are small at birth and develop a postnatal phenotype that closely resembles that of the human metabolic syndrome. Livers of offspring born to MHF mothers also display a fatty phenotype reflecting hepatic steatosis and characteristics of non-alcoholic fatty liver disease. In the present study we hypothesised that a MHF diet leads to altered regulation of liver development in offspring; a derangement that may be detectable during early postnatal life. Livers were collected at postnatal days 2 (P2) and 27 (P27) from male offspring of control and MHF mothers (n = 8 per group). Cell cycle dynamics, measured by flow cytometry, revealed significant G0/G1 arrest in the livers of P2 offspring born to MHF mothers, associated with an increased expression of the hepatic cell cycle inhibitor Cdkn1a. In P2 livers, Cdkn1a was hypomethylated at specific CpG dinucleotides and first exon in offspring of MHF mothers and was shown to correlate with a demonstrable increase in mRNA expression levels. These modifications at P2 preceded observable reductions in liver weight and liver:brain weight ratio at P27, but there were no persistent changes in cell cycle dynamics or DNA methylation in MHF offspring at this time. Since Cdkn1a up-regulation has been associated with hepatocyte growth in pathologic states, our data may be suggestive of early hepatic dysfunction in neonates born to high fat fed mothers. It is likely that these offspring are predisposed to long-term hepatic dysfunction. en
dc.language eng en
dc.publisher Public Library of Science en
dc.relation.ispartofseries PLOS ONE en
dc.rights Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. Details obtained from: en
dc.rights.uri en
dc.rights.uri en
dc.subject Animals en
dc.subject Animals, Newborn en
dc.subject Cell Cycle en
dc.subject DNA Methylation en
dc.subject Dietary Fats en
dc.subject Fatty Liver en
dc.subject Female en
dc.subject Flow Cytometry en
dc.subject Liver en
dc.subject Male en
dc.subject Pregnancy en
dc.subject Prenatal Exposure Delayed Effects en
dc.subject Rats en
dc.title Offspring of mothers fed a high fat diet display hepatic cell cycle inhibition and associated changes in gene expression and DNA methylation. en
dc.type Journal Article en
dc.identifier.doi 10.1371/journal.pone.0021662 en
pubs.issue 7 en
pubs.begin-page e21662 en
pubs.volume 6 en
dc.rights.holder Copyright: Public Library of Science en
dc.identifier.pmid 21779332 en
dc.rights.accessrights en
pubs.subtype Article en
pubs.elements-id 217262 en Liggins Institute en
dc.identifier.eissn 1932-6203 en
dc.identifier.pii PONE-D-11-01388 en
pubs.record-created-at-source-date 2012-03-27 en
pubs.dimensions-id 21779332 en

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