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24 January 2017 Effects of acute exposure to a high-fat, high-sucrose diet on gestational glucose tolerance and subsequent maternal health in mice
Kathleen A. Pennington, Nicola van der Walt, Kelly E. Pollock, Omonseigho O. Talton, Laura C. Schulz
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Abstract

Gestational diabetesmellitus (GDM) is a common obstetric complication. Half of women who have GDM will go on to develop type 2 diabetes. Understanding the mechanisms by which this occurs requires an animal model of GDM without ongoing diabetes at conception. C57Bl/6J mice react acutely to a high-fat, high-sucrose (HFHS) challenge. Here, we hypothesized that a periconceptional HFHS challenge will induce glucose intolerance during gestation. C57Bl/6J femalemice were placed on an HFHS either 1 or 3 weeks prior to mating and throughout pregnancy. Intraperitoneal glucose tolerance tests, insulin measurements, and histological analysis of pancreatic islets were used to assess the impact of acute HFHS. C57Bl/6J females fed HFHS beginning 1 week prior to pregnancy became severely glucose intolerant, with reduced insulin response to glucose, and decreased pancreatic islet expansion during pregnancy compared to control mice. These GDM characteristics did not occur when the HFHS diet was started 3 weeks prior to mating, suggesting the importance of acute metabolic stress. Additionally, HFHS feeding resulted in only mild insulin resistance in nonpregnant females. When the diet was discontinued at parturition, symptoms resolved within 3 weeks. However, mice that experienced glucose intolerance in pregnancy became glucose intolerant more readily in response to a HFHS challenge later in life than congenic females that experienced a normal pregnancy, or that were fed the same diet outside of pregnancy. Thus, acute HFHS challenge in C57Bl/6 mice results in a novel, nonobese, animal model that recapitulates the long-term risk of developing type 2 diabetes following GDM.

Summary Sentence

Exposure to a high-fat, high-sucrose diet just before and during pregnancy in mice impairs islet cell expansion, resulting in glucose intolerance of pregnancy and the development of glucose intolerance later in life.

© The Authors 2017. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please journals.permissions@oup.com
Kathleen A. Pennington, Nicola van der Walt, Kelly E. Pollock, Omonseigho O. Talton, and Laura C. Schulz "Effects of acute exposure to a high-fat, high-sucrose diet on gestational glucose tolerance and subsequent maternal health in mice," Biology of Reproduction 96(2), 435-445, (24 January 2017). https://doi.org/10.1095/biolreprod.116.144543
Received: 24 August 2016; Accepted: 5 January 2017; Published: 24 January 2017
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