Lifestyle Intervention in Preparation for Pregnancy (LIPP)

项目摘要 这项提议的目标是打破肥胖/代谢功能障碍的恶性循环 在怀孕期间。对怀孕期间肥胖女性的生活方式干预效果有限 成功改善母体或子代的短期和长期代谢健康。我们建议 超重和肥胖患者需要在受孕前开始生活方式干预 妇女(以下简称肥胖)首先要改善产妇的新陈代谢。生活方式 干预将在克利夫兰社区娱乐中心进行。新陈代谢 将在凯斯西部保护区的临床研究单位进行评估 临床转化科学中心(CTSC)。这一策略将导致胎儿减少 肥胖和子代代谢功能的改善。我们计划招募200名肥胖女性 追求以下具体目标： 具体目标1：探讨生活方式干预的生理学意义 妊娠准备(LIPP)对孕妇和新生儿代谢及肥胖的影响 人类。 具体目标1a。我们假设先入为主的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、胰岛素反应和能量 与平时护理相比的支出。我们将把母体新陈代谢的这些变化与 胎儿生长(SA1b)。 具体目标1b。我们假设，在开始孕前生活方式干预的女性中 将生下一个出生体重较低、脂肪增加、胰岛素抵抗和 出生时的炎症性症状。身体成分将使用人体测量学和空气测量 置换密度法(豌豆豆荚)。 具体目标2：确定生活方式干预所产生的分子效应 孕前开始改善胎盘线粒体脂质氧化和脂质 积累。 我们假设孕前的生活方式干预会改善胎盘线粒体 氧化，减少脂类的酯化/储存。同位素标记的脂肪酸氧化和 酯化作用将在体外对一部分女性的胎盘外植体进行量化。 采用定量逆转录聚合酶链式反应(qRT-PCR)和酶联免疫吸附试验(ELISA)检测线粒体脂质代谢和含量。 胎盘脂质将用质量分光光度法定量并与新生儿相关 肥胖和母体新陈代谢为SA-1提供了一种机械性的联系.

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.