Placental lipid metabolism impacts fetal adiposity and is programmed by the maternal metabolic milieu in early pregnancy

项目摘要 在美国，五分之一的女性在怀孕期间肥胖(体重指数为30公斤/平方米)。的后代 肥胖女性在晚年患心血管疾病、糖尿病和肥胖的风险更高。这些婴儿经常 出生时有较高的脂肪量和胎盘营养处理的差异可能是导致这些贫穷的原因之一 长期结果。然而，并不是所有的肥胖女性都有肥胖的婴儿，目前还不清楚哪些特定的母亲 胎盘因素会导致婴儿体内脂肪沉积。我们发现肥胖的女性会代谢脂类 不同的是，在怀孕早期，发育中的胎盘对母体的 环境。发育中的婴儿依靠胎盘提供脂肪供应，在怀孕后期， 肥胖女性的胎盘处理脂肪的方式与瘦弱女性不同，这表明向胎盘输送脂肪 宝宝可能会被换掉。这项研究的总体目标是确定母体脂肪代谢如何在早期 怀孕计划胎盘的脂肪代谢和婴儿的脂肪沉积。我们假设肥胖的女性 在怀孕早期脂肪代谢高的人会有独特的脂谱，这些脂类将起到 向发育中的胎盘发出信号，在怀孕早期规划胎盘的脂代谢，并增加 脂肪输送到婴儿和脂肪堆积。为了验证这一假设，我们将招募两组女性。第一 队列将是精瘦和肥胖的女性，我们在整个怀孕期间进行跟踪，测量她们的脂肪代谢，饮食 以及妊娠早期和晚期的身体成分。然后我们将测量胎盘的脂代谢和 他们的婴儿出生时的脂肪质量。在第二组瘦身和肥胖女性中，我们将测量胎盘脂质 妊娠早期的代谢。在这两个队列中，我们将测量特定的母体血脂，这些血脂与 并测试这些脂类对胎盘脂质代谢途径的影响。胎盘代谢 将通过使用同位素标记示踪剂的创新方法进行量化，以识别特定的代谢 受母体脂质信号影响的通路。在完成建议的研究后，我们会确定： 1)在怀孕早期，哪些母体血脂与瘦弱和肥胖妇女的脂肪氧化有关； 2)母体血脂对妊娠早期胎盘脂肪酸代谢的影响；3)机制 母体血脂对胎盘代谢途径和新生儿身体成分的影响 在学期中。这些研究有可能为旨在改善健康状况的营养干预铺平道路。 子孙后代的健康。

Project Abstract One in five women in the US are obese (body mass index (BMI) > 30 kg/m2) during pregnancy. The offspring of obese women are at higher risk of cardiovascular disease, diabetes and obesity in later life. These babies often have a higher fat mass at birth and differences in placental nutrient handling which may contribute to these poor long-term outcomes. However, not all obese women have obese babies and it is unknown what specific maternal and placental factors contribute to fat deposition in babies. We have found that obese women metabolize lipids differently in early pregnancy, a time when the developing placenta is exquisitely sensitive to the maternal environment. The developing baby depends upon the placenta for its lipid supply, and later in pregnancy, placentas of obese women handle fats differently than those of lean women, suggesting that lipid delivery to the baby may be altered. The overall goal of this study is to determine how maternal fat metabolism in early pregnancy programs placental lipid metabolism and a baby's fat deposition. We hypothesize that obese women who have a high fat metabolism in early pregnancy will have a unique lipid profile and these lipids will act as “signals” to the developing placenta, programming placental lipid metabolism in early pregnancy and increasing lipid delivery to the baby and fat accrual. To test this hypothesis, we will recruit two cohorts of women. The first cohort will be lean and obese women that we follow throughout pregnancy, measuring their fat metabolism, diet and body composition in early and again in late pregnancy. We will then measure placental lipid metabolism and their babies' fat mass at birth. In a second cohort of lean and obese women we will measure placental lipid metabolism in early pregnancy. In both cohorts, we will measure specific maternal lipids that are associated with fat metabolism and test the effect of these lipids on placental lipid metabolism pathways. Placental metabolism will be quantified through innovative methods using isotope-labeled tracers to identify specific metabolic pathways affected by maternal lipid signals. Upon completion of the proposed studies we will have determined: 1) which maternal lipids are associated with fat oxidation in lean and obese women in early pregnancy; 2) the effect of maternal lipids on placental fatty acid metabolism in early pregnancy; 3) mechanisms underlying the effect of maternal lipids on placental metabolic pathways and neonatal body composition at term. These studies have the potential to pave the way for nutritional interventions designed to improve the health of future generations.