THE IMPACT OF MATERNAL HEALTH AND DIET ON DEVELOPMENT OF FETAL METABOLIC SYSTEMS

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 在过去20年中，儿童中可预防的代谢性疾病的发病率显著增加。目前，几乎没有信息来确定根本原因，或者治疗或饮食干预是否可以成功预防或减少肥胖妊娠儿童的代谢健康风险。这些研究使用非人灵长类动物（NHP）模型来研究母体代谢健康和饮食不良对发育中胎儿代谢系统发育的影响，以及其产后生长、发育和对饮食诱导的肥胖症和糖尿病的易感性。在这些研究中，育种NHP长期保持高脂肪和高热量饮食（HFD）。这项建议的重点是胎盘，胰腺，肝脏和肌肉，是至关重要的正常调节体重和葡萄糖稳态。该假说认为，从胎盘功能障碍开始的异常直接导致代谢疾病的终生风险。此外，假设补充减少氧化应激和炎症的药剂将预防或减轻妊娠期间在HFD期间观察到的结构、代谢和分子紊乱。我们还在确定含有鱼油或白藜芦醇的膳食补充剂是否能提供类似的保护作用，以防止炎症和氧化应激。这些研究将确定与母亲代谢健康和饮食不良相关的胎儿发育风险和并发症。此外，这些研究将测试膳食补充剂/干预措施，这些措施可以迅速转化为临床，可能有助于预防或减少儿童代谢疾病。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The incidence of preventable metabolic diseases in children has increased markedly over the past 2 decades. Currently, there is little information to determine the underlying causes or whether therapeutic or dietary interventions might be successful at preventing or reducing metabolic health risks in children from obese pregnancy. These studies use a nonhuman primate (NHP) model to investigate the impact of poor maternal metabolic health and diet on the development of metabolic systems in the developing fetus, as well as its postpartum growth, development, and susceptibility to diet induced obesity and diabetes. For these studies, breeding NHPs are chronically maintained on a diet high in fats and calories (HFD). This proposal focuses on the placenta, pancreas, liver and muscle that are critical for normal regulation of body weight and glucose homeostasis. The hypothesis is that abnormalities beginning with placental dysfunction directly contribute to life-long risk for metabolic disease. Furthermore, it is hypothesized that supplementation with agents that reduce oxidative stress and inflammation will prevent or attenuate the structural, metabolic, and molecular disturbances observed during pregnancy while on a HFD. We are also determining if dietary supplements with either fish oil or resveratrol, to prevent inflammation, oxidative stress, will provide similar protection. These studies will identify the risks and complications in the developing fetus associated with poor maternal metabolic health and diet. Furthermore, these studies will test dietary supplements/interventions that can be quickly translated to the clinic that may help prevent or reduce metabolic diseases in children.