University of Tasmania
133344 - Maternal obesity and diabetes induces latent metabolic defects and widespread epigenetic changes in isogenic mice.pdf (4.64 MB)

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

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journal contribution
posted on 2023-05-20, 04:44 authored by Li, CCY, Young, PE, Maloney, CA, Eaton, SA, Cowley, MJ, Buckland, ME, Preiss, T, Darren HenstridgeDarren Henstridge, Cooney, GJ, Febbraio, MA, Martin, DIK, Cropley, JE, Suter, CM
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.


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School of Health Sciences


Taylor & Francis Inc.

Place of publication

United States

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Copyright 2013 Landes Bioscience. Licensed under Creative Commons Attribution-NonCommercial 3.0 Unported (CC BY-NC 3.0)

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  • Open

Socio-economic Objectives

Clinical health not elsewhere classified