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: 8499297
• 负责人: JACOB E FRIEDMAN
• 金额: $ 150.18万
• 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 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8499297
• 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

在过去的两年中，儿童中可预防的代谢性疾病的发病率显著增加。 几十年。目前，几乎没有信息来确定潜在的原因，或者是治疗或 饮食干预可能在预防或降低儿童的代谢健康风险方面取得成功 肥胖怀孕。这些研究将使用非人灵长类动物(NHP)模型来调查贫穷对 母体代谢健康和饮食对发育中胎儿代谢系统发育的影响 由于其产后生长、发育以及对饮食引起的肥胖和糖尿病的易感性。为了这些 研究表明，繁殖的NHP将长期保持高脂肪和高卡路里(HFD)的饮食。国家卫生计划是一项 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， 大脑和胰腺发育。这项建议将侧重于胎盘、胰腺、肝脏和肌肉作为 这些构成了对正常调节体重和血糖至关重要的核心代谢系统。 动态平衡。假设是以胎盘功能障碍开始的异常(即血流， 细胞因子的产生和营养物质的输送)直接影响人体所有代谢系统的发育。 导致终生代谢性疾病风险的后代。此外，还假设 补充减少氧化应激和炎症的药物将防止或减轻 妊娠期间在HFD上观察到的结构、代谢和分子障碍，以及 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 怀孕前从高脂饮食到低脂饮食的彻底改变可以减少或预防 胎儿发育中的并发症。还将确定是否在膳食补充剂中添加鱼油或 白藜芦醇，预防炎症和氧化应激，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发育中胎儿的风险和并发症 和节食。此外，这些研究将测试可以快速翻译的膳食补充剂/干预措施 向临床证明MAV有助于预防或减少儿童代谢性疾病。 相关性(请参阅说明)： 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，导致肥胖和糖尿病增加的潜在并发症和机制 人们对儿童的理解很少。NHP是识别这些机制的关键模型，因为 新陈代谢系统的发育、结构和功能的相似性