The Impact of Maternal Health and Diet on Development of Fetal Metabolic Systems

母亲健康和饮食对胎儿代谢系统发育的影响

基本信息

批准号：
8284456
负责人：
JACOB E FRIEDMAN
金额：
$ 159.58万
依托单位：
OREGON HEALTH & SCIENCE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-09-25 至 2015-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8284456
关键词：
Adolescent Animals Anti-Inflammatory Agents Anti-inflammatory Attenuated Biological Assay Blood flow Body Weight Brain Breeding Calories Carbohydrates Cardiovascular Diseases Cells Child Childhood Chronic Clinic Complex Conceptions Consumption Coupled Data Development Diabetes Mellitus Diet Dietary Fats Dietary Intervention Disease Employee Strikes Epidemic Fat-Restricted Diet Fatty Acids Fatty Liver Fatty acid glycerol esters Fetal Development Fetal Liver Fetus Fish Oils Functional disorder Gene Proteins Gestational Diabetes Glucose Growth and Development function Guidelines Health Hour Human Hypothalamic structure In Vitro Incidence Inflammation Inflammatory Instruction Insulin Resistance Intake Intervention Lead Life Lipids Liver Maternal Health Metabolic Metabolic Diseases Metabolic Pathway Mitochondria Modeling Molecular Mothers Muscle Nature Non obese Non-Insulin-Dependent Diabetes Mellitus Nutrient Obesity Organ Outcome Overweight Oxidative Stress Pancreas Pattern Physiological Placenta Postpartum Period Predisposition Pregnancy Prevention Primates Principal Investigator Production Publishing Reducing Agents Regulation Resveratrol Risk Signal Transduction Skeletal Muscle Staging Structure Supplementation System Techniques Testing Therapeutic Intervention Time Translating adenylate kinase base blood glucose regulation cytokine dietary supplements early onset endocrine pancreas development fetal hepatic gluconeogenesis in vivo lipid metabolism mitochondrial dysfunction mother nutrition nonhuman primate obesity in children offspring oxidative damage pancreas development postnatal prevent programs protective effect therapy design

项目摘要

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 will 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 will be chronically maintained on a diet high in fats and calories (HFD). The NHP is a critical model as it shares developmental features similar to human fetuses, including placental function, brain, and pancreas development. This proposal will focus on the placenta, pancreas, liver and muscle as these form the core metabolic systems that are critical for normal regulation of body weight and glucose homeostasis. The hypothesis is that abnormalities beginning with placental dysfunction (i.e., blood flow, cytokine production and nutrient delivery) directly impact the development of all metabolic systems in the offspring that 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, and will prevent the abnormal development of metabolic systems in primate offspring. These studies will determine if a complete dietary switch from the HFD to a low fat diet just prior to pregnancy can reduce or prevent complications in fetal development. It will also be determined 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. Futhermore, these studies will test dietary supplements/interventions that can be quickly translated to the clinic that mav help prevent or reduce metabolic diseases in children. RELEVANCE (See instructions): Poor maternal health and nutrition are associated with an increased risk of metabolic diseases in children. However, the underlying complications and mechanisms that lead to the increase in obesity and diabetes in children is poorly understood. The NHP is a critical model to identify these mechanisms because ofthe simlarities in development, as well as structure and function of metabolic systems

过去2年儿童可预防代谢性疾病发病率明显上升几十年。目前，几乎没有信息可以确定根本原因或是否有治疗或治疗作用。饮食干预可能会成功预防或降低儿童代谢健康风险肥胖怀孕。这些研究将使用非人类灵长类动物 (NHP) 模型来调查贫困人口的影响母亲的代谢健康和饮食对发育中的胎儿代谢系统的发育也有影响因为其产后生长、发育以及对饮食引起的肥胖和糖尿病的易感性。对于这些研究表明，繁殖中的 NHP 将长期维持高脂肪和高热量饮食 (HFD)。 NHP 是一个关键模型，因为它具有与人类胎儿相似的发育特征，包括胎盘功能，大脑和胰腺的发育。该提案将重点关注胎盘、胰腺、肝脏和肌肉这些形成了核心代谢系统，对于体重和血糖的正常调节至关重要体内平衡。假设是异常始于胎盘功能障碍（即血流、细胞因子的产生和营养物质的输送）直接影响体内所有代谢系统的发育导致后代终生罹患代谢疾病的风险。此外，假设补充减少氧化应激和炎症的药物将预防或减轻怀孕期间服用 HFD 时观察到的结构、代谢和分子紊乱，并且会防止灵长类后代代谢系统的异常发育。这些研究将确定是否在怀孕前从高脂饮食完全转变为低脂饮食可以减少或预防胎儿发育的并发症。还将确定膳食补充剂是否含有鱼油或白藜芦醇可以预防炎症、氧化应激，提供类似的保护。这些研究将确定与母亲代谢健康状况不佳相关的发育中胎儿的风险和并发症和饮食。此外，这些研究将测试可以快速转化的膳食补充剂/干预措施向诊所表明mav有助于预防或减少儿童代谢性疾病。相关性（参见说明）：孕产妇健康和营养不良与儿童代谢疾病风险增加有关。然而，导致肥胖和糖尿病增加的潜在并发症和机制孩子们理解甚少。 NHP 是识别这些机制的关键模型，因为发育以及代谢系统的结构和功能的相似性