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Offspring from maternal nutrient restriction in mice show variations in adult glucose metabolism similar to human fetal growth restriction

Published online by Cambridge University Press:  03 December 2018

B. N. Radford  and
V. K. M. Han
B. N. Radford
Affiliation:
Department of Biochemistry, Schulich School of Medicine & Dentistry, Western University, London, ON, Canada Children’s Health Research Institute, London, ON, Canada
V. K. M. Han*
Affiliation:
Department of Biochemistry, Schulich School of Medicine & Dentistry, Western University, London, ON, Canada Children’s Health Research Institute, London, ON, Canada Department of Pediatrics, Schulich School of Medicine & Dentistry, Western University, London, ON, Canada
*
Address for correspondence: V.K.M. Han, MD, Children’s Health Research Institute, Victoria Hospital, 800 Commissioners Rd E, London, ON, Canada N6A 5W9. E-mail: Victor.Han@lhsc.on.ca
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Abstract

Fetal growth restriction (FGR) is a pregnancy condition in which fetal growth is suboptimal for gestation, and this population is at increased risk for type 2 diabetes as adults. In humans, maternal malnutrition and placental insufficiency are the most common causes of FGR, and both result in fetal undernutrition. We hypothesized that maternal nutrient restriction (MNR) in mice will cause FGR and alter glucose metabolism in adult offspring. Pregnant CD-1 mice were subjected to MNR (70% of average ad libitum) or control (ad libitum) from E6.5 to birth. Following birth, mice were fostered by mothers on ad libitum feeds. Weight, blood glucose, glucose tolerance and tissue-specific insulin sensitivity were assessed in male offspring. MNR resulted in reduced fetal sizes but caught up to controls by 3 days postnatal age. As adults, glucose intolerance was detected in 19% of male MNR offspring. At 6 months, liver size was reduced (P = 0.01), but pAkt-to-Akt ratios in response to insulin were increased 2.5-fold relative to controls (P = 0.004). These data suggest that MNR causes FGR and long-term glucose intolerance in a population of male offspring similar to human populations. This mouse model can be used to investigate the impacts of FGR on tissues of importance in glucose metabolism.

Keywords

fetal growth restrictionglucose metabolisminsulin sensitivityliver

Information

Type
Original Article
Information
Journal of Developmental Origins of Health and Disease , Volume 10 , Issue 4 , August 2019 , pp. 469 - 478
Copyright
© Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2018 

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