Volume 597, Issue 23 p. 5619-5637
Research Paper
Free to Read

Prenatal alcohol exposure programmes offspring disease: insulin resistance in adult males in a rat model of acute exposure

Tam M. T. Nguyen

Tam M. T. Nguyen

School of Biomedical Sciences, The University of Queensland, St Lucia, QLD, Australia

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Sarah E. Steane

Sarah E. Steane

School of Biomedical Sciences, The University of Queensland, St Lucia, QLD, Australia

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Karen M. Moritz

Karen M. Moritz

School of Biomedical Sciences, The University of Queensland, St Lucia, QLD, Australia

Child Health Research Centre, The University of Queensland, South Brisbane, QLD, Australia

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Lisa K. Akison

Corresponding Author

Lisa K. Akison

School of Biomedical Sciences, The University of Queensland, St Lucia, QLD, Australia

Child Health Research Centre, The University of Queensland, South Brisbane, QLD, Australia

Corresponding author L. K. Akison: Child Health Research Centre, The University of Queensland, Room 408, Centre for Children's Health Research (CCHR), 62 Graham St, South Brisbane, QLD 4101, Australia. Email: [email protected]Search for more papers by this author
First published: 08 October 2019
Citations: 19

Edited by: Laura Bennet & Janna Morrison

This article was first published as a preprint: Nguyen TMT, Steane BT, Moritz KM and Akison LK (2019). Prenatal alcohol exposure programs offspring disease: Insulin resistance in adult males in a rat model of acute exposure. bioRxiv. https://doi.org/10.1101/684639.

Linked articles: This article is highlighted in a Perspectives article by Gatford. To read this article, visit https://doi.org/10.1113/JP279051.

All of the underlying data used in the figures and tables reported in this study can be accessed from the following URL: https://doi.org/10.5281/zenodo.3406863.

This is an Editor's Choice article from the 1 December 2019 issue.

Abstract

Key points

  • Prenatal alcohol exposure has the potential to affect fetal development and programme chronic disease in offspring.
  • Previous preclinical models typically use high, chronic doses of alcohol throughout pregnancy to examine effects on offspring, particularly on the brain and behaviour.
  • In this study we use a rat model of moderate, acute, prenatal alcohol exposure to determine if this can be detrimental to maintenance of glucose homeostasis in adolescent and adult offspring.
  • Although female offspring were relatively unaffected, there was evidence of insulin resistance in 6-month-old male offspring exposed to prenatal alcohol, suggestive of a pre-diabetic state.
  • This result suggests that even a relatively low-dose, acute exposure to alcohol during pregnancy can still programme metabolic dysfunction in a sex-specific manner.

Alcohol consumption is highly prevalent amongst women of reproductive age. Given that approximately 50% of pregnancies are unplanned, alcohol has the potential to affect fetal development and programme chronic disease in offspring. We examined the effect of an acute but moderate prenatal alcohol exposure (PAE) on glucose metabolism, lipid levels and dietary preference in adolescent and/or adult rat offspring. Pregnant Sprague–Dawley rats received an oral gavage of ethanol (1 g kg−1 maternal body weight, n = 9 dams) or an equivalent volume of saline (control, n = 8 dams) at embryonic days 13.5 and 14.5. PAE resulted in a blood alcohol concentration of 0.05–0.06% 1 h post-gavage in dams. Fasting blood glucose concentration was not affected by PAE in offspring at any age, nor were blood glucose levels during a glucose tolerance test (GTT) in 6-month-old offspring (> 0.5). However, there was evidence of insulin resistance in PAE male offspring at 6 months of age, with significantly elevated fasting plasma insulin (= 0.001), a tendency for increased first phase insulin secretion during the GTT and impaired glucose clearance following an insulin challenge (= 0.007). This was accompanied by modest alterations in protein kinase B (AKT) signalling in adipose tissue. PAE also resulted in reduced calorie consumption by offspring compared to controls (= 0.04). These data suggest that a relatively low-level, acute PAE programmes metabolic dysfunction in offspring in a sex-specific manner. These results highlight that alcohol consumption during pregnancy has the potential to affect the long-term health of offspring.