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

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 在过去的20年里，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能成功地预防或减少肥胖怀孕儿童的代谢健康风险。这些研究使用非人灵长类动物(NHP)模型来研究不良的母体代谢健康和饮食对发育中的胎儿代谢系统的影响，以及产后的生长发育和对饮食引起的肥胖和糖尿病的易感性。在这些研究中，繁殖的NHP长期维持在高脂肪和高卡路里(HFD)的饮食中。这项建议侧重于胎盘、胰腺、肝脏和肌肉，这些对正常调节体重和血糖稳态至关重要。假设是，以胎盘功能障碍开始的异常直接导致了代谢性疾病的终生风险。此外，假设补充减少氧化应激和炎症的药物将防止或减轻怀孕期间在HFD上观察到的结构、代谢和分子障碍。我们还在确定添加鱼油或白藜芦醇的膳食补充剂是否会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发育中胎儿的风险和并发症。此外，这些研究将测试可以迅速转化为临床的有助于预防或减少儿童代谢性疾病的膳食补充剂/干预措施。

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.