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患有肥胖症（体重指数 (BMI) > 30 kg/m2）。 肥胖女性在以后的生活中患心血管疾病、糖尿病和肥胖的风险更高。 出生时脂肪量较高，胎盘营养处理方面存在差异，这可能导致这些贫困人口 然而，并非所有肥胖女性都会产生肥胖婴儿，而且尚不清楚具体是什么母亲。 胎盘因素会导致婴儿脂肪沉积。我们发现肥胖女性会代谢脂质。 怀孕早期的情况有所不同，此时胎盘正在发育，对母体非常敏感。 婴儿的发育环境依赖于胎盘的脂质供应，并且在怀孕后期， 肥胖女性的胎盘处理脂肪的方式与瘦女性的胎盘不同，这表明脂质输送到胎盘 这项研究的总体目标是确定母亲早期脂肪代谢的情况。 怀孕计划胎盘脂质代谢和婴儿的脂肪沉积。 妊娠早期脂肪代谢较高的人将具有独特的脂质特征，这些脂质将充当 向发育中的胎盘发出“信号”，在妊娠早期规划胎盘脂质代谢并增加 为了检验这一假设，我们将招募两组女性。 队列将是我们在整个怀孕期间跟踪的瘦和肥胖女性，测量她们的脂肪代谢、饮食 然后，我们将测量胎盘脂质代谢和怀孕早期和晚期的身体成分。 在第二组瘦和肥胖女性中，我们将测量她们的婴儿出生时的脂肪量。 在这两个队列中，我们将测量与妊娠早期代谢相关的特定母体脂质。 脂肪代谢并测试这些脂质对胎盘脂质代谢途径的影响。 将通过创新方法进行量化，使用同位素标记的示踪剂来识别特定的代谢 完成拟议的研究后，我们将确定： 1) 哪些母体脂质与妊娠早期瘦和肥胖女性的脂肪氧化有关； 2）母体血脂对妊娠早期胎盘脂肪酸代谢的影响；3）机制； 母体脂质对胎盘代谢途径和新生儿身体成分影响的基础 这些研究有可能为旨在改善足月的营养干预措施铺平道路。 子孙后代的健康。