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：
8147743
负责人：
JACOB E FRIEDMAN
金额：
$ 163.52万
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/8147743
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 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 public health relevance therapy design

项目摘要

DESCRIPTION (provided by applicant): 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. Furthermore, 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. PUBLIC HEALTH RELEVANCE: 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 of the similarities in development, as well as structure and function of metabolic systems

描述（由申请人提供）：在过去的20年中，儿童可预防的代谢疾病的发生率显着增加。当前，几乎没有信息可以确定基本原因，或者是否可以成功地防止或减少肥胖怀孕儿童的代谢健康风险，是否可以成功地进行治疗或饮食干预措施。这些研究将使用非人类灵长类动物（NHP）模型来研究不良的代谢健康和饮食对发育中胎儿代谢系统发展的影响，以及其产后生长，发育，饮食诱导肥胖和糖尿病的易感性。对于这些研究，NHP的繁殖将长期维持在高脂肪和卡路里（HFD）的饮食中。 NHP是一个关键模型，因为它具有类似于人类胎儿的发育特征，包括胎盘功能，大脑和胰腺发育。该建议将集中于胎盘，胰腺，肝脏和肌肉，因为这些构成了核心代谢系统，这对于正常调节体重和葡萄糖稳态至关重要。假设是，异常是从胎盘功能障碍（即血流，细胞因子产生和养分递送）开始的，直接影响后代所有代谢系统的发展，这有助于终身对代谢疾病的风险。此外，假设补充降低氧化应激和炎症的药物会预防或减轻HFD期间怀孕期间观察到的结构，代谢和分子障碍，并防止灵长类动物后代中代谢系统的异常发展。这些研究将确定在怀孕前从HFD转换为低脂饮食的完整切换可以减少或防止胎儿发育并发症。还将确定是否饮食中的鱼油或白藜芦醇可以防止炎症，氧化应激，将提供类似的保护。这些研究将确定与不良的孕产妇代谢健康和饮食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快速转化为诊所的饮食补充剂/干预措施，该诊所有助于预防或减少儿童代谢疾病。公共卫生相关性：孕产妇健康和营养差与儿童代谢疾病的风险增加有关。但是，对儿童肥胖和糖尿病增加的潜在并发症和机制知之甚少。 NHP是识别这些机制的关键模型，因为开发的相似性以及代谢系统的结构和功能