Owens J A, Thavaneswaran P, De Blasio M J, McMillen I C, Robinson J S, Gatford K L
Research Centre for Reproductive Health, Discipline of Obstetrics and Gynaecology, School of Paediatrics and Reproductive Health, University of Adelaide, Adelaide, SA 5005, Australia.
Am J Physiol Endocrinol Metab. 2007 Jun;292(6):E1879-89. doi: 10.1152/ajpendo.00706.2006. Epub 2007 Feb 27.
Prenatal and early postnatal life experiences, reflected by size at birth and postnatal catch-up growth, contribute to the risk of developing the metabolic syndrome in adulthood, but their relative importance is unclear. Therefore, we determined the effects of restricted placental and fetal growth on components of the metabolic syndrome in young adult sheep and the relationships of the latter to size at birth and early postnatal growth. Fasting plasma metabolites, glucose tolerance (by intravenous glucose tolerance test, IVGTT), insulin secretion and sensitivity, and resting blood pressure were measured in 22 control and 20 placentally restricted (PR) 1-yr-old sheep. In male sheep, PR increased the initial rise in glucose during an IVGTT and reduced diastolic blood pressure, and small size at birth independently predicted reduced adult size, glucose tolerance, and fasting plasma insulin and insulin disposition of glucose metabolism but increased insulin disposition of circulating FFAs. Also in males, high fractional growth rates in early postnatal life independently predicted impaired early glucose clearance during an IVGTT. In female animals, PR increased insulin sensitivity of glucose metabolism and reduced fasting plasma FFAs, and thinness at birth predicted increased adult size, fasting blood glucose, and pulse pressure. In conclusion, PR and small size at birth are associated with more components of the metabolic syndrome in adult male than in adult female sheep, with few independent effects of early postnatal growth. These sex differences in the onset and extent of adverse metabolic consequences after prenatal restraint in the sheep are consistent with observations in humans.
产前和产后早期的生活经历，通过出生时的体重和产后追赶生长反映出来，会增加成年后患代谢综合征的风险，但其相对重要性尚不清楚。因此，我们确定了胎盘和胎儿生长受限对年轻成年绵羊代谢综合征各组分的影响，以及后者与出生时体重和产后早期生长的关系。对22只对照羊和20只胎盘生长受限（PR）的1岁绵羊测量了空腹血浆代谢物、葡萄糖耐量（通过静脉葡萄糖耐量试验，IVGTT）、胰岛素分泌和敏感性以及静息血压。在雄性绵羊中，PR增加了IVGTT期间葡萄糖的初始上升幅度，并降低了舒张压，出生时体型小独立预测成年体型减小、葡萄糖耐量降低、空腹血浆胰岛素水平降低以及葡萄糖代谢的胰岛素处置能力降低，但循环中游离脂肪酸（FFA）的胰岛素处置能力增加。同样在雄性中，出生后早期的高分生长率独立预测IVGTT期间早期葡萄糖清除受损。在雌性动物中，PR增加了葡萄糖代谢的胰岛素敏感性，并降低了空腹血浆FFA水平，出生时体重轻预测成年体型增大、空腹血糖升高和脉压升高。总之，与成年雌性绵羊相比，成年雄性绵羊中PR和出生时体型小与代谢综合征的更多组分相关，产后早期生长的独立影响较少。绵羊产前受限后不良代谢后果的发生和程度的这些性别差异与人类的观察结果一致。
