The Developmental Origins of Health and Disease Hypothesis states that the in utero environment influences postnatal health and plays a role in disease etiology. In humans, exposure to maternal obesity in utero increases diabetes susceptibility in the offspring. In the U.S., it is estimated that about half of pregnancies occur in overweight or obese mothers. Thus, the consequences of maternal obesity will be manifested in future generations. Animal models have demonstrated that exposure to maternal high-fat-diet (HFD) feeding or obesity results in morphological alterations in the pancreatic islets, as well as impaired expression of islet transcription factors in the offspring. However, effects of in utero diet exposure often vary significantly between animal models. In a non-human primate (NHP) model of maternal overnutrition, we have demonstrated that fetuses exposed to HFD have reduced islet hormone transcript levels and increased β:α cell ratio due to decreased α-cell mass. This increase in β:α cell ratio persists post-weaning out to three years only when offspring are maintained on a HFD. However, maternal or post-weaning diet does not affect endocrine cell proliferation or β-cell mass in this model. Preliminary data in a mouse model of maternal overnutrition suggests that mice exposed to HFD are glucose intolerant shortly after weaning onto control diet, but have no differences in β-cell mass. When mice are aged to 12-weeks-old, the difference in glucose tolerance is no longer apparent, and body weight is not different between HFD-exposed and control mice. Data from the NHP model suggests that maternal HFD exposure results in subtle alterations in islet structure that persist only when offspring are maintained on HFD. In the mouse, impairments in glucose tolerance shortly after weaning are resolved when offspring are maintained on a control, lower-fat diet until 12 weeks of age.


J. Elsakr: None. P. Kievit: Research Support; Self; Novo Nordisk A/S, Janssen Research & Development. A.C. Powers: None. M.A. Gannon: None. R. Bottino: None. D.L. Takahashi: None.

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