Lifestyle Intervention in Preparation for Pregnancy (LIPP)

项目摘要 这项建议的目的是打破肥胖/代谢功能障碍的恶性循环 孕期在怀孕期间对肥胖妇女的生活方式干预有限， 成功改善母亲或后代的短期和长期代谢健康。我们提出 生活方式干预需要在超重和肥胖者受孕前开始， 妇女（以下简称肥胖），以首先改善产妇的新陈代谢。生活方式 干预措施将在克利夫兰社区娱乐中心进行。代谢 评估将在凯斯西储的临床研究部门进行 临床转化科学中心（CTSC）。这一策略将导致胎儿减少 肥胖和改善后代的代谢功能。我们计划招募200名肥胖女性 实现以下具体目标： 具体目标1：探讨生活方式干预在老年人中的生理意义。 妊娠准备（LIPP）对孕产妇和新生儿代谢和肥胖的影响 人类 具体目标1a.我们假设，孕前生活方式干预将有助于降低 母体胰岛素抵抗、炎症、体重、肥胖、肠促胰岛素反应和能量 与常规护理相比。我们将把母体代谢的这些变化与 胎儿生长（SA 1b）。 具体目标1b。我们假设，在妇女开始孕前生活方式干预， 将产生一个出生体重较低、脂肪堆积、胰岛素抵抗的婴儿， 出生时的炎症特征。身体成分将使用人体测量和空气测量 位移密度测定法（Pea Pod）。 具体目标2：确定生活方式干预的分子效应 在怀孕前开始改善胎盘线粒体脂质氧化和脂质 积累 我们假设，怀孕前的生活方式干预将改善胎盘线粒体 氧化和减少脂质酯化/储存。同位素标记的脂肪酸氧化和 将在来自一部分妇女的胎盘外植体中体外定量酯化。 将使用qRT-PCR和Elisa测量线粒体脂质代谢和含量。 胎盘脂质将通过质量分光光度法定量，并与新生儿 肥胖和母体代谢提供了与SA 1的机制联系。

Project Summary The objective of this proposal is to break the vicious cycle of obesity/metabolic dysfunction during pregnancy. Lifestyle interventions in obese women during pregnancy have had limited success in improving maternal or offspring short and long-term metabolic health. We propose that lifestyle interventions need to be initiated prior to conception in overweight and obese women (henceforth referred to as obese) in order to first improve maternal metabolism. Lifestyle interventions will take place in the Cleveland Community Recreation Centers. Metabolic evaluations will be conducted in the Clinical Research Units of the Case Western Reserve Clinical Translational Science Center (CTSC). This strategy will result in decreased fetal adiposity and improved metabolic function in the offspring. We plan to recruit 200 obese women to pursue the following specific aims: Specific Aim 1: To investigate the physiological significance of lifestyle intervention in preparation for pregnancy (LIPP) on maternal and neonatal metabolism and adiposity in humans. Specific Aim 1a. We hypothesize that preconception lifestyle intervention will facilitate lower maternal insulin resistance, inflammation, weight, adiposity, incretin response and energy expenditure compared to usual care. We will link these changes in maternal metabolism with fetal growth (SA1b). Specific Aim 1b. We hypothesize that in women initiating pre-pregnancy lifestyle intervention will deliver a baby with lower birth weight and fat accretion, insulin resistance, and inflammatory profile at birth. Body composition will be measured using anthropometrics and air displacement densitometry (Pea Pod). Specific Aim 2: To determine the molecular effects whereby lifestyle intervention initiated before pregnancy improves placental mitochondrial lipid oxidation and lipid accumulation. We hypothesize that lifestyle intervention before pregnancy will improve placental mitochondrial oxidation and decrease lipid esterification/storage. Isotope-labeled fatty acid oxidation and esterification will be quantified in vitro in placental explants from a subset of women. Mitochondrial lipid metabolism and content will be measured using qRT-PCR and Elisa. Placental lipids will be quantified by mass spectrophotometry and correlated with neonatal adiposity and maternal metabolism providing a mechanistic link to SA 1.