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: 10475293
• 负责人: Raziel Rojas-Rodriguez
• 金额: $ 1.77万
• 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 2022-12-05
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10475293
• 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.

项目概要 全球卫生机构报告称，他们对女性怀孕人数不断增加的趋势表示担忧 超重或肥胖以及妊娠期体重增加过多（GWG）的母亲的后续研究。 后代二元组显示母亲孕前体重指数 (BMI) 和 GWG 之间的关联 作为后代发育的重要因素，儿童肥胖症的患病率不断上升是一个公众关注的问题。 健康很重要，因为肥胖儿童在成年后很可能保持肥胖状态并患上与以下疾病相关的疾病 临床研究表明，妊娠前母亲与生命早期代谢综合征之间存在关联。 肥胖与婴儿肥胖和心脏代谢风险之间存在潜在的机制联系 营养过剩导致胎儿过度生长，以及肥胖、2 型糖尿病和心血管疾病的高风险 因此，预防儿童肥胖应从干预孕前母亲BMI开始。 为该奖学金提出的研究项目是随机对照试验“生活方式”的辅助研究 怀孕准备干预”(LIPP) 干预的目标（地中海饮食和指导）。 运动）旨在促进超重/肥胖女性在计划怀孕前减轻 5-7% 的体重，以改善体重 母体代谢和减少新生儿肥胖的益处来自临床研究的证据已经报道。 体重减轻 5-10% 可以改善脂肪组织 (AT) 的胰岛素敏感性，但是 AT 的分子变化 需要确定在该体重减轻范围内驱动胰岛素敏感性增强的辅助措施。 研究旨在提供干预措施对母体脂肪细胞葡萄糖纵向影响的经验数据 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）、随机分组后 6 个月以及怀孕早期获得。 纵向变化将与身体成分、静息能量等临床代谢参数相关 除了母体研究之外，我还会进行支出、炎症和胰岛素抵抗的血清标志物。 研究干预措施是否有益地影响脐带间充质的代谢程序 我将利用 ucMSC 脂肪分化 (ad-ucMSC) 新技术作为干细胞。 新生儿脂肪细胞功能指数，并确定计划怀孕前的生活方式干预是否会增强 ad-ucMSC 的胰岛素敏感性和改善脂质代谢是一个独特的机会。 研究孕前生活方式干预对母亲 AT 代谢功能的纵向影响 获得的研究结果将检查潜在的早期生物标志物和机制作为预测因素。 后代的长期代谢结果。