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

胎盘脂质代谢影响胎儿肥胖，并受妊娠早期母体代谢环境影响

• 批准号: 9397888
• 负责人: Perrie F O'Tierney-Ginn
• 金额: $ 9.53万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-13 至 2018-03-01
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9397888
• 关键词: Adult Children; Affect; Air; Birth; Body Composition; Body mass index; Cardiovascular Diseases; Child; Cross-Sectional Studies; Data; Densitometry; Deposition; Development; Diabetes Mellitus; Diet; Dietary Intervention; Elderly; Environment; Esterification; Fasting; Fatty Acids; Fatty acid glycerol esters; Fetus; Future Generations; Genes; Goals; Growth; Health; High Risk Woman; Hyperlipidemia; In Vitro; Incidence; Insulin Resistance; Isotope Labeling; Lipid A; Lipids; Longitudinal prospective study; Mass Spectrum Analysis; Measures; Metabolic; Metabolic Pathway; Metabolism; Methods; Mothers; Neonatal; Nutrient; Obesity; Outcome; Oxidative Stress; Oxides; PPAR gamma; Pathway interactions; Peroxisome Proliferator-Activated Receptors; Pisum sativum; Placenta; Placentation; Plasma; Polyunsaturated Fatty Acids; Pregnancy; Prevalence; Recruitment Activity; Research; Research Design; Role; Signal Transduction; Signaling Molecule; Testing; Thinness; Time; Tracer; Variant; Woman; base; cohort; diabetes risk; disorder risk; fatty acid metabolism; fetal; fetus nutrition; high risk; improved; innovation; lipid biosynthesis; lipid mediator; lipid metabolism; lipid transport; maternal obesity; metabolic phenotype; metabolic profile; neonatal outcome; novel; nutrient metabolism; obesity risk; offspring; oxidation; oxidized lipid; placental transfer; programs; response; therapy design; transcription factor

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.

项目摘要 美国五分之一的女性在怀孕期间肥胖（体重指数（BMI）> 30 kg/m2）。的后代 肥胖妇女在晚年患心血管疾病、糖尿病和肥胖症的风险更高。这些婴儿经常 出生时脂肪量较高，胎盘营养处理的差异可能导致这些不良 长期成果。然而，并不是所有的肥胖妇女都有肥胖的婴儿， 胎盘因素会导致婴儿脂肪沉积。我们发现肥胖妇女代谢脂质 不同的是，在怀孕早期，发育中的胎盘对母体的反应非常敏感。 环境发育中的婴儿依赖胎盘提供脂质，在怀孕后期， 肥胖妇女的胎盘处理脂肪的方式与瘦妇女不同，这表明向胎盘输送脂肪的方式与瘦妇女不同。 宝宝可能会改变。这项研究的总体目标是确定母亲的脂肪代谢如何在早期 怀孕程序胎盘脂质代谢和婴儿的脂肪沉积。我们假设肥胖女性 在怀孕早期脂肪代谢高的女性会有一个独特的脂质分布，这些脂质会作为 “信号”的发展胎盘，编程胎盘脂质代谢在怀孕早期和增加 脂质输送到婴儿和脂肪积累。为了验证这一假设，我们将招募两组女性。第一 队列将是瘦和肥胖的妇女，我们在整个怀孕期间跟踪，测量她们的脂肪代谢，饮食 和身体成分的变化。然后我们将测量胎盘脂质代谢， 婴儿出生时的脂肪量在第二个队列的瘦和肥胖妇女中，我们将测量胎盘脂质 怀孕早期的新陈代谢。在这两个队列中，我们将测量特定的母体脂质， 脂肪代谢，并测试这些脂质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途径。在完成拟议的研究后，我们将确定： 1)母体脂质与妊娠早期瘦和肥胖妇女的脂肪氧化有关; 2)孕早期母体脂质对胎盘脂肪酸代谢的影响; 3）机制 母体脂质对胎盘代谢途径和新生儿身体组成的影响 在学期中。这些研究有可能为营养干预铺平道路， 子孙后代的健康。