Effects of acute exposure to a high-fat, high-sucrose diet on gestational glucose tolerance and subsequent maternal health in mice†

Abstract

Gestational diabetes mellitus (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 female mice 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.

The effects of myo-inositol and probiotic supplementation in a high-fat-fed preclinical model of glucose intolerance in pregnancy

“…The aim of the present study was to determine whether MI and PB, taken together or separately before and during pregnancy, would impact the development of HFD-induced glucose intolerance during pregnancy (22) . This mouse model allowed a factorial design to determine the interaction of treatments, as well as more thorough examination of potential mechanistic pathways and whole-tissue analysis, which would not be possible in human trials.…”

“…They remained on their allocated diet/treatment throughout mating and pregnancy. HFD 1 week prior to and throughout pregnancy has been previously demonstrated to produce an effective mouse model of gestational-specific glucose intolerance (22) . Mice were checked daily by inspection of the vagina for a cervical plug.…”

“…the present study is an adaptation of a mouse model previously developed by Pennington et al (22) . We chose this model because our original model of choice, the heterozygous LepR db/þ mouse, did not display glucose intolerance, as discussed in detail in our previous publications (38,39) .…”

Maternal hyperglycemia and fetal cardiac development: Clinical impact and underlying mechanisms

“…Note that, a similar association with CHD was not seen in a different genetic background when exposed to HFD for a shorter period of time (Schulkey et al, ). Studies using STZ, HFD, and high‐fat high‐sucrose diet‐induced rodent models have also been carried out to examine maternal pathologies during late onset of DM during pregnancy or GDM that may affect fetal outcomes (Pasek & Gannon, ; Pennington, van der Walt, Pollock, Talton, & Schulz, ). Additionally, the influence of specific genetic background on the propensity to develop each types of diabetes has also been recognized in mouse models (Leiter, ; Wolf, Lilly, & Shin, ).…”

In Utero and Postnatal Exposure to High Fat, High Sucrose Diet Suppressed Testis Apoptosis and Reduced Sperm Count

“…However, the effect of in utero exposure to maternal diabetes on fertility of male offspring has not been studied. We have developed an animal model of gestational glucose intolerance, in which C57BL/6J dams are fed a high fat, high sucrose diet from 1 week pre-gestation through the end of pregnancy 20 . Under this acute HFHS exposure, dams fail to expand beta cell numbers during pregnancy, leading to an inadequate insulin response to glucose challenge, and glucose intolerance during mid-late pregnancy 20 .…”