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

Dudley, Kevin J., Sloboda, Deborah M., Connor, Kristin L., Beltrand, Jacques and Vickers, Mark H. (2011) Offspring of mothers fed a high fat diet display hepatic cell cycle inhibition and associated changes in gene expression and DNA methylation. PLoS One, 6 7: e21662.1-e21662.8. doi:10.1371/journal.pone.0021662


Author Dudley, Kevin J.
Sloboda, Deborah M.
Connor, Kristin L.
Beltrand, Jacques
Vickers, Mark H.
Title Offspring of mothers fed a high fat diet display hepatic cell cycle inhibition and associated changes in gene expression and DNA methylation
Journal name PLoS One   Check publisher's open access policy
ISSN 1932-6203
Publication date 2011-07
Sub-type Article (original research)
DOI 10.1371/journal.pone.0021662
Open Access Status DOI
Volume 6
Issue 7
Start page e21662.1
End page e21662.8
Total pages 8
Place of publication San Francisco, CA, United States
Publisher Public Library of Science
Collection year 2012
Language eng
Formatted 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.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status Non-UQ
Additional Notes Article # e21662

Document type: Journal Article
Sub-type: Article (original research)
Collections: Non HERDC
Queensland Brain Institute Publications
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 48 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 58 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Fri, 21 Oct 2011, 12:17:57 EST by Kevin Dudley on behalf of Queensland Brain Institute