Maternal obesity accelerates fetal pancreatic β-cell but not α-cell development in sheep: prenatal consequences
Maternal obesity accelerates fetal pancreatic β-cell but not α-cell development in sheep: prenatal consequences
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DOI：
10.1152/ajpregu.00072.2009
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发表时间：
2009-09-01
影响因子：
2.8
通讯作者：
Nijland, Mark J.
中科院分区：
文献类型：
--
作者：
Ford, Stephen P.;Zhang, Liren;Nijland, Mark J.
Ford SP, Zhang L, Zhu M, Miller MM, Smith DT, Hess BW, Moss GE, Nathanielsz PW, Nijland MJ。母体肥胖加速绵羊胎儿胰腺β细胞发育，但不加速α细胞发育：产前后果。[J] .中国生物医学工程学报，2009,31(2):559 - 563。首次发表于2009年7月15日；doi: 10.1152 / ajpregu.00072.2009。-母亲肥胖会影响后代体重、身体组成和器官功能，增加患糖尿病和代谢综合征的风险。我们确定了母亲肥胖和高能量饮食对胎儿胰腺发育的影响。在繁殖前60天，母羊被分配到对照饲粮[100%的国家研究委员会（NRC）建议]或致肥饲粮（OB; 150% NRC）。在妊娠75天，OB母羊在休息和葡萄糖耐量试验中表现出较高的胰岛素-葡萄糖比率，与对照母羊相比表现出胰岛素抵抗。在胎儿研究中，母羊在怀孕前60天到怀孕后75天吃各自的饮食，这些动物在全身麻醉下被安乐死。从饲粮开始到尸检，OB母羊和对照母羊的体重分别增加了43%和6%。虽然OB母羊胎儿的所有器官都较重，但只有胰腺重量占胎儿体重的百分比有所增加。妊娠第75天，OB母羊和胎儿的血糖、胰岛素和皮质醇均升高。由于β细胞有丝分裂增加而非程序性细胞死亡减少，OB母羊胎儿的每单位胰腺面积胰岛素阳性细胞增加50%。OB母羊的羔羊出生较早，但体重与对照羔羊相同；然而，它们的冠臀长度减少，脂肪量增加。我们得出结论，OB母羊胎儿全身胰岛素增加是由于葡萄糖暴露增加和/或皮质醇诱导的胎儿β细胞成熟加速，并可能导致后代β细胞功能过早丧失，易患肥胖和代谢疾病。
Ford SP, Zhang L, Zhu M, Miller MM, Smith DT, Hess BW, Moss GE, Nathanielsz PW, Nijland MJ. Maternal obesity accelerates fetal pancreatic beta-cell but not alpha-cell development in sheep: prenatal consequences. Am J Physiol Regul Integr Comp Physiol 297: R835-R843, 2009. First published July 15, 2009; doi: 10.1152/ajpregu.00072.2009.-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 similar to 43% and similar to 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 beta-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 beta-cell maturation and may contribute to premature beta-cell function loss and predisposition to obesity and metabolic disease in offspring.