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

• 批准号: 8703085
• 负责人: JACOB E FRIEDMAN
• 金额: $ 153.34万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-25 至 2015-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8703085
• 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

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

儿童可预防的代谢性疾病的发病率在过去2年中显著增加， 几十年目前，几乎没有信息来确定根本原因或是否治疗或 饮食干预可能会成功地预防或减少儿童的代谢健康风险， 肥胖妊娠。这些研究将使用非人类灵长类动物（NHP）模型来调查贫困的影响。 母亲的代谢健康和饮食对发育中的胎儿代谢系统的发展，以及 由于其产后的生长、发育和易患饮食诱发的肥胖症和糖尿病。为这些 在研究中，育种NHP将长期保持高脂肪和高热量的饮食（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， 大脑和胰腺的发育这项提案将集中在胎盘，胰腺，肝脏和肌肉， 这些形成了对体重和葡萄糖的正常调节至关重要的核心代谢系统 体内平衡假设是从胎盘功能障碍开始的异常（即，血流， 细胞因子的产生和营养输送）直接影响所有代谢系统的发展， 导致终生代谢疾病风险的后代。此外，据推测， 补充减少氧化应激和炎症的试剂将预防或减轻 妊娠期间服用HFD时观察到的结构、代谢和分子紊乱， 防止灵长类后代新陈代谢系统的异常发育。这些研究将确定， 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。还将确定是否含有鱼油或 白藜芦醇，防止炎症，氧化应激，将提供类似的保护。这些研究将 确定与母亲代谢健康不良相关的胎儿发育风险和并发症 和饮食。此外，这些研究将测试膳食补充剂/干预措施，可以迅速转化为 可以帮助预防或减少儿童代谢性疾病。 相关性（参见说明）： 产妇健康和营养不良与儿童患代谢性疾病的风险增加有关。 然而，潜在的并发症和机制，导致肥胖和糖尿病的增加， 孩子们很难理解。NHP是识别这些机制的关键模型，因为 发育的相似性以及代谢系统的结构和功能