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The Effects on In Utero Western Style Diet on the Endocrine Pancreas of the Offspring

dc.contributor.advisorO'Brien, Richard
dc.creatorElsakr, Joseph 2020
dc.description.abstractThe Developmental Origins of Health and Disease (DOHaD) Hypothesis postulates that the in utero environment influences postnatal health and plays a role in disease etiology. Studies in humans and animal models have demonstrated that an environment of in utero overnutrition leads to increased risk of metabolic disease such has Type 2 Diabetes in the offspring. However, the mechanisms by which this increased risk is transmitted are not well understood. In rodent models, maternal obesity or high fat diet (HFD) can lead to changes in islet cell composition and function. In order to investigate the effects of maternal overnutrition in an animal model similar to humans, a non-human primate model with similar islet composition and function to humans is utilized. A maternal Western-style diet (WSD) high in fat, sucrose, and cholesterol results in weight gain and hyperinsulinemia in dams. While WSD does not lead to impaired glucose tolerance during pregnancy, offspring glucose tolerance tended to correlate with maternal glucose tolerance. Islets from offspring exposed to maternal WSD had reduced α-cell mass and enhanced glucose-stimulated insulin secretion ex vivo at both one and three years of age. Increased insulin secretion was associated with a few changes in islet gene expression, but no changes in mitochondrial mass, oxidative capacity, or insulin granule density. In a mouse model of maternal HFD, offspring exposed to HFD had no changes in glucose tolerance or endocrine cell mass. Thus, the effects of maternal overnutrition in these animal models is subtle, but the phenotypes observed are consistent with previous studies in this model and observed at multiple time points. Additional deleterious effects of maternal overnutrition may only manifest with increased age or additional metabolic stress in the offspring.
dc.subjectdevelopmental origins, diabetes, primate
dc.titleThe Effects on In Utero Western Style Diet on the Endocrine Pancreas of the Offspring
dc.type.materialtext University Graduate School

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