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Maternal obesity and diabetes induces latent metabolic defects and widespread epigenetic changes in isogenic mice

Citation

Li, CCY and Young, PE and Maloney, CA and Eaton, SA and Cowley, MJ and Buckland, ME and Preiss, T and Henstridge, DC and Cooney, GJ and Febbraio, MA and Martin, DIK and Cropley, JE and Suter, CM, Maternal obesity and diabetes induces latent metabolic defects and widespread epigenetic changes in isogenic mice, Epigenetics, 8, (6) pp. 602-611. ISSN 1559-2294 (2013) [Refereed Article]


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Copyright 2013 Landes Bioscience. Licensed under Creative Commons Attribution-NonCommercial 3.0 Unported (CC BY-NC 3.0) https://creativecommons.org/licenses/by-nc/3.0/

DOI: doi:10.4161/epi.24656

Abstract

Intrauterine nutrition can program metabolism, creating stable changes in physiology that may have significant health consequences. The mechanism underlying these changes is widely assumed to involve epigenetic changes to the expression of metabolic genes, but evidence supporting this idea is limited. Here we have performed the first study of the epigenomic consequences of exposure to maternal obesity and diabetes. We used a mouse model of natural-onset obesity that allows comparison of genetically identical mice whose mothers were either obese and diabetic or lean with a normal metabolism. We find that the offspring of obese mothers have a latent metabolic phenotype that is unmasked by exposure to a Western-style diet, resulting in glucose intolerance, insulin resistance and hepatic steatosis. The offspring show changes in hepatic gene expression and widespread but subtle alterations in cytosine methylation. Contrary to expectation, these molecular changes do not point to metabolic pathways but instead reside in broadly developmental ontologies. We propose that, rather than being adaptive, these changes may simply produce an inappropriate response to suboptimal environments; maladaptive phenotypes may be avoidable if postnatal nutrition is carefully controlled.

Item Details

Item Type:Refereed Article
Keywords:cytosine methylation, diabetes, epigenetic programming, fetal programming, obesity, leptin, animal experiment, animal model, animal tissue, article, controlled study, copy number variation, diabetes mellitus, DNA methylation, female, gene expression
Research Division:Biological Sciences
Research Group:Biochemistry and cell biology
Research Field:Cell metabolism
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:Henstridge, DC (Mr Darren Henstridge)
ID Code:133344
Year Published:2013
Web of Science® Times Cited:52
Deposited By:Health Sciences
Deposited On:2019-06-24
Last Modified:2019-07-23
Downloads:8 View Download Statistics

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