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

孕前生活方式干预对孕产妇和新生儿脂肪细胞代谢的影响

• 批准号: 10326337
• 负责人: Raziel Rojas-Rodriguez
• 金额: $ 6.64万
• 依托单位: TUFTS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-30 至 2023-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10326337
• 关键词: Adipocytes; Adipose tissue; Adult; Ancillary Study; Automobile Driving; Biopsy; Blood; Body Composition; Body Weight decreased; Body fat; Body mass index; Cardiovascular Diseases; Cell Size; Cellular Metabolic Process; Child; Childhood; Clinical; Clinical Research; Conceptions; Data; Development; Disease; Energy Metabolism; Enrollment; Environment; Exercise; Fatty Acids; Fatty acid glycerol esters; Fellowship; Fetal Growth; Fetal Macrosomia; Fetus; Follow-Up Studies; Funding; Glucose; Goals; Health; Healthy Eating; Hyperinsulinism; Impairment; In Vitro; Inflammation; Inflammatory; Insulin Resistance; Intervention; Life; Link; Lipids; Lipolysis; Measures; Mediterranean Diet; Mesenchymal Stem Cells; Metabolic; Metabolic Pathway; Metabolic syndrome; Metabolism; Molecular; Mothers; Neonatal; Newborn Infant; Non-Insulin-Dependent Diabetes Mellitus; Nutrient; Obesity; Outcome; Overnutrition; Overweight; Phenotype; Planned Pregnancy; Postpartum Period; Pregnancy; Pregnant Women; Preparation; Prevalence; Prevention; Public Health; Randomized; Randomized Controlled Trials; Reporting; Research; Research Project Grants; Rest; Serum; Serum Markers; Supervision; Techniques; Testing; Thinness; Triglycerides; Umbilical cord structure; United States National Institutes of Health; Weight; Woman; adipocyte differentiation; basal insulin; cardiometabolic risk; comparison intervention; diet and exercise; early detection biomarkers; early pregnancy; fatty acid oxidation; gestational weight gain; global health; glucose metabolism; glucose uptake; high risk; improved; in utero; indexing; infant adiposity; inflammatory marker; insulin sensitivity; interest; intervention effect; lifestyle intervention; lipid metabolism; maternal obesity; metabolic profile; newborn adiposity; novel; obese mothers; obesity in children; obesity risk; obesogenic; offspring; prepregnancy; progenitor; stem cells; translational study; treatment as usual; trend

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.

项目总结 全球卫生机构报告称，他们对女性怀孕人数增加的趋势感到担忧 超重或肥胖，并有过多的妊娠体重增加(GWG)。对母亲的后续研究- 研究表明，孕妇孕前体重指数(BMI)与GWG之间存在关联 作为后代发育的重要贡献者。儿童肥胖症患病率的上升是一个公共问题 健康问题，因为肥胖儿童可能在成年后保持肥胖，并患上与以下疾病相关的疾病 生命早期的代谢综合征。临床研究表明，孕前母体与 肥胖与婴儿肥胖和心脏代谢风险之间可能存在机制联系 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的BMI开始。 本次奖学金的研究项目是随机对照试验“生活方式”的辅助研究。 准备怀孕的干预措施“(理柏)。干预的目标(地中海饮食和导游 运动)是促进超重/肥胖女性在计划怀孕前减重5%-7%以改善 减少母体新陈代谢和新生儿肥胖。来自临床研究的证据已经报告了这种益处。 体重减轻5-10%改善脂肪组织(AT)的胰岛素敏感性，但AT的分子变化 需要确定在这个减肥范围内导致胰岛素敏感性增强的原因。建议的附属设施 这项研究试图为干预对母体脂肪细胞血糖的纵向影响提供经验数据 和脂类代谢以及炎症状态。分析将利用臀肌AT活组织检查完成 在研究登记时(基线)、随机后6个月和怀孕早期获得。分子 纵向变化将与身体成分、静息能量等临床代谢参数相关 支出，以及炎症和胰岛素抵抗的血清标志物。除了母性研究，我还会 探讨干预是否有益于影响脐带间充质的代谢规划 干细胞(UcMSC)。我将利用ucMSC成脂分化的新技术(ad-ucMSC)作为 新生儿脂肪细胞功能指数和计划妊娠前生活方式干预是否增强 改善ad-ucMSC的胰岛素敏感性和脂代谢。拟议的研究是一个独特的机会 探讨孕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。所获得的发现将检验潜在的早期生物标志物和作为预测因素的机制。 子代的长期新陈代谢结果。