METABOLISM IN THE NONHUMAN PRIMATE AND OVINE FETUS

胎儿能量储备的增加是一个必要的准备， 子宫外的生命，但负责这种积累的机制 并没有得到很好的理解。 这项建议的论点是， 胎盘基质转运和代谢与胎盘激素 分泌，为糖原生成编程胎儿环境， 脂肪生成 我们将研究胎盘功能，基质 可用性和胎盘催乳素作用，以便将 很明显胎盘控制的胎儿环境 胎儿的能量储备 直接从葡萄糖，从 肝内糖酵解过程中衍生的前体， 循环前体将在胎羊中定量， 狒狒 生烃途径发展的时间进程 糖原生成与糖原的积累有关， 胎/新生大鼠。 假设乳酸和谷氨酰胺， 由胎盘代谢葡萄糖和谷氨酸产生 分别是糖原生成前体， （生热途径），这些物质的可用性 将测试循环前体增强胎儿糖生成。 绵羊胎盘催乳素（大鼠肝细胞）是否间接增强 糖原生成，以及人类胎盘催乳素是否具有类似的 将确定影响（狒狒胎肝细胞）。 的 将检查脂肪生成的前体。 的假设 乳酸盐和谷氨酰胺增强胎儿脂肪生成并减少 将在体外测试脂解作用（大鼠，狒狒肝细胞/狒狒 脂肪细胞）。 人胎盘催乳素对胎儿的影响 将在体外评估脂肪生成/脂肪分解。 总脂肪生成 在狒狒体内测量酮体的脂肪生成 胎儿 酮体和谷氨酸的转移和代谢将 在灌注的足月人胎盘中定量，以便 确认其经胎盘通过和代谢的性质。 这些研究直接关系到人类的福祉 新生儿，因为胎儿能量储存的获取是至关重要的， 在分娩期间以及在丧失胎儿 脐能量供应和开始口服摄入。 一个 了解胎儿发育的生理机制 能源储存将允许合理的管理和理解 生长迟缓的新生儿和糖尿病的婴儿 女人 它将帮助我们了解禁食的影响 酮病和母体营养过剩对胎儿的影响。

The accrual of fetal energy stores is a necessary preparation for extrauterine life, but the mechanisms responsible for this accrual are not well understood. The thesis of this proposal is that placental substrate transport and metabolism, and placental hormone secretion, program the fetal milieu for glycogenesis and lipogenesis. We will study placental function, substrate availability, and placental lactogen action, in order to relate clearly the placentally-controlled fetal milieu to the development of fetal energy stores. Glycogenesis directly from glucose, from precursors derived during intrahepatic glycolysis, and from circulating precursors will be quantitated in fetal sheep and baboons. The time course of development of the gluconeogenic path to glycogenesis will be correlated with accrual of glycogen in the fetal/neonatal rat. The hypothesis that lactate and glutamine, produced by placental metabolism from glucose and glutamate respectively, are glycogenic precursors through the indirect (gluconeogenic route), and that the availability of these circulating precursors enhances fetal glycogenesis will be tested. Whether ovine placental lactogen (rat hepatocyte) enhances indirect glycogenesis, and whether human placental lactogen has similar effects (baboon fetal hepatocyte) will be determined. The precursors for lipogenesis will be examined. The hypothesis that lactate and glutamine enhance fetal lipogenesis and diminish lipolysis will be tested in vitro (rat, baboon hepatocyte/baboon adipocyte). The effect of human placental lactogen on fetal lipogenesis/lipolysis will be assessed in vitro. Total lipogenesis and lipogenesis from ketone bodies will be measured in the baboon fetus. Transfer and metabolism of ketone bodies and glutamate will be quantitated in the perfused, term human placenta, in order to confirm the nature of their transplacental passage and metabolism. These studies have direct bearing on the well-being of the human neonate, since acquisition of fetal energy stores is essential for survival during delivery and during the time between loss of the umbilical energy supply and commencement of oral intake. An understanding of the physiologic mechanisms involved in fetal energy storage will permit rational management and understanding of the growth-retarded neonate, and the infant of the diabetic woman. It will help us to understand the effects of fasting ketosis and of maternal nutritional oversupply upon the fetus.