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

Cheryl C.Y. Li, Paul E. Young, Christopher A. Maloney, Sally A. Eaton, Mark J. Cowley, Michael E. Buckland, Thomas Preiss, Darren C. Henstridge, Gregory J Cooney, Mark A. Febbraio, David I.K. Martin, Jennifer E. Cropley, Catherine M Suter

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45 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)602-611
Number of pages10
JournalEpigenetics
Volume8
Issue number6
DOIs
Publication statusPublished - 1 Jun 2013
Externally publishedYes

Keywords

  • Cytosine methylation
  • Diabetes
  • Epigenetic programming
  • Fetal programming
  • Obesity

Cite this

Li, C. C. Y., Young, P. E., Maloney, C. A., Eaton, S. A., Cowley, M. J., Buckland, M. E., ... Suter, C. M. (2013). Maternal obesity and diabetes induces latent metabolic defects and widespread epigenetic changes in isogenic mice. Epigenetics, 8(6), 602-611. https://doi.org/10.4161/epi.24656
Li, Cheryl C.Y. ; Young, Paul E. ; Maloney, Christopher A. ; Eaton, Sally A. ; Cowley, Mark J. ; Buckland, Michael E. ; Preiss, Thomas ; Henstridge, Darren C. ; Cooney, Gregory J ; Febbraio, Mark A. ; Martin, David I.K. ; Cropley, Jennifer E. ; Suter, Catherine M. / Maternal obesity and diabetes induces latent metabolic defects and widespread epigenetic changes in isogenic mice. In: Epigenetics. 2013 ; Vol. 8, No. 6. pp. 602-611.
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Li, CCY, Young, PE, Maloney, CA, Eaton, SA, Cowley, MJ, Buckland, ME, Preiss, T, Henstridge, DC, Cooney, GJ, Febbraio, MA, Martin, DIK, Cropley, JE & Suter, CM 2013, 'Maternal obesity and diabetes induces latent metabolic defects and widespread epigenetic changes in isogenic mice', Epigenetics, vol. 8, no. 6, pp. 602-611. https://doi.org/10.4161/epi.24656

Maternal obesity and diabetes induces latent metabolic defects and widespread epigenetic changes in isogenic mice. / Li, Cheryl C.Y.; Young, Paul E.; Maloney, Christopher A.; Eaton, Sally A.; Cowley, Mark J.; Buckland, Michael E.; Preiss, Thomas; Henstridge, Darren C.; Cooney, Gregory J; Febbraio, Mark A.; Martin, David I.K.; Cropley, Jennifer E.; Suter, Catherine M.

In: Epigenetics, Vol. 8, No. 6, 01.06.2013, p. 602-611.

Research output: Contribution to journalArticleResearchpeer-review

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