In Wisconsin, nearly 30 percent of those giving birth have obesity, which increases the risk of adverse outcomes for both parent and child. There is an urgent need for evidence on safe, effective weight loss recommendations before pregnancy to help reduce the intergenerational risk of diabetes and improve maternal-child health outcomes. This project compared four preconception weight loss strategies using mouse models. Both dietary change and bariatric surgery were sufficient for inducing weight loss and improving body composition before pregnancy, but breeding difficulties and loss of pups hindered the ability to assess how the different weight loss methods affect milk fat production and offspring pancreatic health. The project has been proven viable and is well-positioned for further work.
The Challenge
Obesity before pregnancy increases the risk of complications such as gestational diabetes, preeclampsia and adverse outcomes for both parent and child. In Wisconsin, nearly 30 percent of people giving birth have obesity, underscoring the need for effective preconception interventions. However, weight loss before pregnancy is difficult to achieve and maintain.
Project Goals
The goal of this project was to compare preconception weight loss strategies to assess their effects on weight loss efficacy and maintenance, gestational glycemia, milk fat composition and offspring pancreatic health.
Results
The researcher successfully generated obesity in female mice through 20 weeks of high fat diet, despite their known resistance to diet-induced obesity. The mice then entered one of four treatment groups: high fat diet continuation, healthy diet transition, vertical sleeve gastrectomy (VSG) with a healthy diet, or GLP-1 drug with a healthy diet. The dose of GLP-1 drug resulted in a rapid, unsustainable weight loss in the mice and was discontinued after two weeks. By the end of the five-week treatment phase, the healthy diet and VSG groups had significant reductions in body weight and fat mass compared to the high fat diet-maintained group. Data also suggests that VSG surgery before pregnancy contributes to greater improvement in glucose tolerance during pregnancy compared to switching to a healthy diet alone.
An unanticipated high rate of early postnatal deaths led to insufficient numbers for the milk collection protocol. Since there were not enough litters to assess differences in milk lipid composition between preconception weight loss strategies, the researcher instead used this as an opportunity to refine the milk collection technique. Due to these challenges, there were not any pups available for phenotyping as young adults to assess offspring postnatal health and propensity for metabolic disease. Postnatal data collected until day 16, although underpowered, showed similar blood glucose between groups. There is a trend toward smaller body weight, pancreas weight, and heart weight in the pups of VSG-treated mice pups. The study clarified areas for methodological changes to retain the GLP-1 arm, increase breeding success and increase sample size.
