Location: Arthropod-borne Animal Diseases ResearchTitle: Maternal Obesity Accelerates Fetal Pancreatic Beta Cell but not Alpha Cell Development in the Sheep: Prenatal and Postnatal Consequences Author
Submitted to: American Journal of Physiology - Regulatory Integrative & Comparative Physiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/29/2009
Publication Date: 7/15/2009
Publication URL: http://ajpregu.physiology.org/content/297/3/R835.full.pdf+html
Citation: Ford, S.P., Zhang, L., Zhu, M., Miller, M.M., Smith, D.T., Hess, B.W., Moss, G.E., Nathanielsz, P.W., Nijland, M.J. 2009. Maternal Obesity Accelerates Fetal Pancreatic Beta Cell but not Alpha Cell Development in the Sheep: Prenatal and Postnatal Consequences. American Journal of Physiology. Interpretive Summary: Obesity in the mother affects the weight and health of the offspring, including the risk for developing diabetes. We determined the effects of a high energy diet and obesity in the mother on the development of the fetal pancreas. Fetuses from obese ewes had a higher pancreas weight and 50% more insulin secreting cells than fetuses from control ewes. Obese ewes and their fetuses had elevated blood sugar, insulin and cortisol. Lambs from fat ewes were born earlier and had more fat mass than those born to control ewes. We conclude that increased blood sugar levels in fetuses from obese ewes leads to more insulin secreting cells and increased blood insulin. This may contribute to premature loss of insulin secreting cells and predisposition to diabetes in the offspring.
Technical Abstract: Maternal obesity affects offspring weight, body composition and organ function, increasing diabetes and metabolic syndrome risk. We determined effects of maternal obesity and a high energy diet on fetal pancreatic development. Sixty days prior to breeding. ewes were assigned to control (C, 100% of NRC recommendations) or obesogenic (OB, 150% NRC) diets. At 75 days gestation OB ewes exhibited elevated insulin:glucose ratios at rest and during a glucose tolerance test, demonstrating insulin resistance compared with C ewes. In fetal studies ewes ate their respective diets from 60 days before to 75 days after conception when animals were euthanized under general anesthesia. OB and C ewes increased in body weight by ~ 43 % and ~6 % respectively from diet initiation until necropsy. Although all organs were heavier in fetuses from OB ewes, only pancreatic weight increased as a percentage of fetal weight. Blood glucose, insulin and cortisol were elevated in OB ewes and fetuses on day 75. Insulin positive cells/unit pancreatic area were 50% greater in fetuses from OB ewes, as a result of increased beta cell mitoses rather than decreased programmed cell death. Lambs of OB ewes were born earlier but weighed the same as C lambs; however, their crown-rump length was reduced, and their fat mass was increased. We conclude that increased systemic insulin in fetuses from OB ewes results from increased glucose exposure, and/or cortisol-induced accelerated fetal beta cell maturation and may contribute to premature beta cell function loss and predisposition to diabetes in offspring.