The impact of lifestyle interventions prior to pregnancy on maternal and neonatal adipocyte metabolism

项目摘要 全球卫生机构报告说，他们对妇女怀孕的增加趋势感到关切， 超重或肥胖且妊娠期体重过度增加（GWG）。母亲的后续研究- 后代的二对儿显示了母亲孕前体重指数（BMI）和GWG之间的关联 对后代的发育有着重要的影响儿童肥胖症的日益流行是一个公众 健康问题，因为肥胖儿童可能在成年后仍然肥胖，并发展与肥胖相关疾病， 代谢综合征的早期症状临床研究表明，妊娠前母亲 肥胖与婴儿肥胖和心脏代谢风险，提示子宫内肥胖与婴儿肥胖和心脏代谢风险之间可能存在机械联系。 营养过剩与胎儿过度生长和肥胖，2型糖尿病和心血管疾病的高风险， 后代因此，预防儿童肥胖首先要从孕前干预母亲BMI开始。 该研究计划是一项随机对照试验“生活方式”的辅助研究 准备怀孕的干预措施”（LIPP）。干预的目标（地中海饮食和指导 运动）是促进超重/肥胖妇女在计划怀孕前减轻5-7%的体重， 降低母体代谢和新生儿肥胖。来自临床研究的证据已经报道了 5-10%的体重减轻对改善脂肪组织（AT）胰岛素敏感性的影响，然而AT的分子变化 需要确定在该范围内的体重减轻中驱动增强的胰岛素敏感性。拟议的辅助 一项研究旨在提供干预对母体脂肪细胞葡萄糖的纵向影响的经验数据 和脂质代谢以及炎症状态。将利用臀肌AT活检进行分析 在研究入组（基线）、随机化后6个月和妊娠早期获得。分子 纵向变化将与身体成分、静息能量、代谢水平和代谢水平等临床代谢参数相关。 以及炎症和胰岛素抵抗的血清标志物。除了母亲的研究，我会 研究干预是否有益地影响脐带间充质干细胞的代谢程序， 干细胞（ucMSC）。我将利用ucMSC成脂分化（ad-ucMSC）的新技术， 新生儿脂肪细胞功能指数并确定计划怀孕前生活方式干预是否能增强 胰岛素敏感性和改善脂代谢。拟议的研究是一个独特的机会， 调查妊娠前生活方式干预对母体AT代谢功能的纵向影响， 新生儿肥胖症获得的发现将检查潜在的早期生物标志物和机制作为预测因子 后代的长期代谢结果。

PROJECT SUMMARY Global health agencies have reported their concern on the increasing trend in women entering pregnancy as either overweight or obese and having excessive gestational weight gain (GWG). Follow-up studies of mother- offspring dyads have shown the association between maternal prepregnancy body mass index (BMI) and GWG as significant contributors to offspring development. The increasing prevalence in childhood obesity is a public health matter since obese children are likely to stay obese in adulthood and develop diseases associated with the metabolic syndrome earlier in life. Clinical studies have demonstrated the associations of pregravid maternal obesity with infant adiposity and cardiometabolic risk, suggesting a possible mechanistic link between in utero overnutrition with fetal overgrowth and high risk of obesity, type-2 diabetes and cardiovascular disease in the offspring. Therefore, prevention of childhood obesity begins with interventions on maternal BMI before gestation. The research project proposed for this fellowship is an ancillary study of the randomized controlled trial “Lifestyle Interventions in Preparation for Pregnancy” (LIPP). The goal of the intervention (Mediterranean diet and guided exercise) is to promote a 5-7% weight loss before a planned pregnancy in overweight/obese women to improve maternal metabolism and reduce neonatal adiposity. Evidence from clinical research has reported the benefits of 5-10% weight loss on improving adipose tissue (AT) insulin sensitivity, however the molecular changes in AT driving enhanced insulin sensitivity in this range of weight loss need to be determined. The proposed ancillary study seeks to provide empirical data on the longitudinal effects of the intervention on maternal adipocyte glucose and lipid metabolism as well as the inflammatory state. The analysis will be done utilizing gluteal AT biopsies obtained at study enrollment (baseline), 6 months after randomization, and in early pregnancy. The molecular longitudinal changes will be associated with clinical metabolic parameters of body composition, resting energy expenditure, and serum markers of inflammation and insulin resistance. In addition to the maternal studies, I will investigate if the intervention beneficially impacts the metabolic programming of umbilical cord mesenchymal stem cells (ucMSC). I will utilize the novel technique of ucMSC adipogenic differentiation (ad-ucMSC) as an index of neonatal adipocyte function and determine if lifestyle interventions prior to a planned pregnancy enhance insulin sensitivity and improve lipid metabolism of ad-ucMSC. The proposed research is a unique opportunity to investigate the longitudinal effects of pregravid lifestyle interventions on maternal AT metabolic function and neonatal adiposity. The findings obtained will examine potential early biomarkers and mechanisms as predictors of long-term metabolic outcomes in the offspring.