Models of gestational diabetes and offspring outcomes in mice
Abstract
Gestational diabetes mellitus (GDM) is the most common pregnancy disorder. GDM pregnancies result in offspring that are more likely to develop metabolic syndrome in adolescence than the background population. As offspring experience these adverse effects during their reproductive years, GDM has the potential to propagate disease for many generations. Hyperleptinemia, a key characteristic of both GDM and maternal obesity has not been studied in isolation to determine its role in programming offspring outcomes. Hyperglycemia in the absence of obesity has also not been widely modeled without surgical or chemical means. My research goal was to study the offspring outcomes of these two facets of GDM in C57B6 mice. We observed that maternal hyperleptinemia improved offspring insulin sensitivity, and protected the offspring from developing glucose intolerance. These outcomes were partly mediated by reduced fatty acid accumulation in the liver. Our findings suggest that maternal hyperleptinemia is protective of offspring glucose control. Maternal hyperglycemia in lean dams increased offspring adiposity while glucose tolerance was unchanged. This effect was mediated by a preference for glucose over lipids for substrate utilization, and multiple gene expression changes in the male adipose tissue and liver. Our results indicate that lean maternal hyperglycemia results in metabolically healthy obesity in offspring. This work demonstrates that GDM in lean women may not negatively affect glucose tolerance, and that maternal hyperleptinemia may mediate this, through improving insulin sensitivity. It supports other data that suggest that the liver and adipose tissue are key regulators of whole body metabolism.
Degree
Ph. D.
Thesis Department
Rights
OpenAccess.
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