TY - JOUR
T1 - Maternal obesity accelerates fetal pancreatic β-cell but not α-cell development in sheep
T2 - Prenatal consequences
AU - Ford, Stephen P.
AU - Zhang, Liren
AU - Zhu, Meijun
AU - Miller, Myrna M.
AU - Smith, Derek T.
AU - Hess, Bret W.
AU - Moss, Gary E.
AU - Nathanielsz, Peter W.
AU - Nijland, Mark J.
PY - 2009/9
Y1 - 2009/9
N2 - 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 [100% of National Research Council (NRC) recommendations] or obesogenic (OB; 150% NRC) diets. At 75 days gestation, OB ewes exhibited elevated insulin-to-glucose ratios at rest and during a glucose tolerance test, demonstrating insulin resistance compared with control 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 control 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 per unit pancreatic area were 50% greater in fetuses from OB ewes as a result of increased β-cell mitoses rather than decreased programmed cell death. Lambs of OB ewes were born earlier but weighed the same as control lambs; however, their crown-to-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 β-cell maturation and may contribute to premature β-cell function loss and predisposition to obesity and metabolic disease in offspring.
AB - 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 [100% of National Research Council (NRC) recommendations] or obesogenic (OB; 150% NRC) diets. At 75 days gestation, OB ewes exhibited elevated insulin-to-glucose ratios at rest and during a glucose tolerance test, demonstrating insulin resistance compared with control 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 control 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 per unit pancreatic area were 50% greater in fetuses from OB ewes as a result of increased β-cell mitoses rather than decreased programmed cell death. Lambs of OB ewes were born earlier but weighed the same as control lambs; however, their crown-to-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 β-cell maturation and may contribute to premature β-cell function loss and predisposition to obesity and metabolic disease in offspring.
KW - Fetal growth
KW - Pancreatic function
KW - Sheep
UR - http://www.scopus.com/inward/record.url?scp=69249110098&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=69249110098&partnerID=8YFLogxK
U2 - 10.1152/ajpregu.00072.2009
DO - 10.1152/ajpregu.00072.2009
M3 - Article
C2 - 19605766
AN - SCOPUS:69249110098
VL - 297
SP - R835-R843
JO - American Journal of Physiology
JF - American Journal of Physiology
SN - 0363-6119
IS - 3
ER -