Developmental Programming by Mismatch of Pre-and Postnatal Nurtition

产前和产后营养不匹配导致的发育规划

基本信息

批准号：
8328700
负责人：
PETER W. NATHANIELSZ
金额：
$ 77.17万
依托单位：
UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-09-05 至 2016-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8328700
关键词：
Address Adult Advertising Animal Model Animals Applications Grants Archives Area Award Birth Body Composition Books Breeding Cardiovascular system Cells Cessation of life Chile Chronic Chronic Disease Cohort Studies Commit Communities Complex Congresses Control Animal Control Groups DEXA Data Deltastab Development Diabetes Mellitus Diagnostic Diet Disease Dual-Energy X-Ray Absorptiometry Eating Elderly Endocrine Environment Environmental Risk Factor Epidemiologist Epidemiology Epigenetic Process Exposure to Family Fatty acid glycerol esters Female Fetal Growth Fetal Growth Retardation Fetal Reduction Fetus Food Funding Future Gene Expression Glucocorticoids Glucose Goals Health Hormones Human Human Development Human Resources Institutes Lactation Letters Life Metabolic Metabolism Molecular Profiling Monoclonal Antibody R24 Mothers National Center for Research Resources National Children&apos s Study National Heart, Lung, and Blood Institute National Institute of Allergy and Infectious Disease National Institute of Child Health and Human Development National Institute of Diabetes and Digestive and Kidney Diseases National Institute of Environmental Health Sciences National Institute of Mental Health National Institute of Neurological Disorders and Stroke Neonatal Newborn Infant Non-Insulin-Dependent Diabetes Mellitus Nutrient Nutritional Obesity Outcome Papio Perinatal Exposure Phenotype Phosphoenolpyruvate Carboxylase Physical activity Pituitary-Adrenal System Pregnancy Research Research Design Research Personnel Resource Sharing Resources Rodent Somatotropin Therapeutic Time Tissues Translating United States National Institutes of Health Weaning Weight Work Writing animal facility authority cohort cost feeding fetal gene environment interaction innovation interest male mother nutrition neonate nonhuman primate novel nutrition offspring peripheral blood postnatal programs response social

项目摘要

DESCRIPTION (provided by applicant): Developmental Programming (DP) defined as - responses to challenges in a critical window of fetal or neonatal life that alter normal development with resulting persistent effects on phenotype, modifies phenotype by gene-environment interaction. In rodents, maternal nutrient reduction (MNR) in pregnancy (P) leads to fetal nutrient reduction (FNR), which may be compounded by restriction in lactation (L) predisposing offspring (OFF) to obesity and other chronic conditions. OFF of MNR mothers in P develop a thrifty phenotype to better survive if poor post-natal nutrition follows FNR. - A "predictive adaptive response." FNR in rodents, mismatched by excess (or even normal) neonatal nutrition also predisposes OFF to chronic disease. In an R24 addressing MNR (MNR R24) we developed baboon OFF cohorts of 1) control (CTR) baboons fed ad lib in P and L - CTR/CTR (P diet first, L second) and 2) MNR baboons fed 70% global weight adjusted CTR (MNR/MNR). This R24 only finished in June 2009. In the year since, 11 grant applications have been submitted - six successfully. A second R24 to develop cohorts of OFF of mothers fed a high energy diet (HED) producing dietary induced maternal obesity (MO) in P and L (MO/MO, MO R24) began February 2010. Specific Aim: To develop cohorts of nonhuman primate (NHP) OFF exposed to nutrient mismatch (MM) in fetal and neonatal life - MNR/CTR and MNR/MO as a multi-investigator resource to study mechanisms (MM R24). We are committed to developing cohorts to compare mechanisms underlying human DP. We now have three cohorts- CTR/CTR, MNR/MNR, MO/MO. Of the six other potential cohorts three, CTR/MNR, CTR/MO and MO/MNR hold little interest. We propose to develop cohorts of MNR/CTR and MNR/MO because, as the several letters we include show, mismatch is central to DP- two authorities even entitle their book Mismatch. Approach: We control food intake, maintaining normal social and physical activity. The recently funded MO R24 provides contemporaneous CTR pregnancies for this MM R24 if funded - a 33% saving in cost. During P baboons of similar phenotype will be fed 70% of CTR (MNR). After birth, MNR mothers are fed ad lib either chow or HED. After weaning all OFF eat chow. Thirteen new letters (all from outside San Antonio, 4 outside USA) are added to the 24 prior letters showing wide-spread interest in studying these cohorts. We also separately provide 13 letters from leading DP epidemiologists supporting NHP work. Environment, Investigators and Innovation: PIs and SFBR provide a unique combination of facilities, animals and expertise for this work. PIs have held collaborative NHLBI, NICHD, NEI, NINCDS, NIA NIMH, NIDDK funding since 1976. Extensive MM studies exist on altricial species but not precocial NHP in which key pre- natal and neonatal environmental factors - P02, glucose, hormones are very different. The proposed MM R24 plus three on-going cohorts provide novel opportunities in DP relevant to multiple NIH institutes (NHLBI, NIDDK, NICHD, NIAID, NEI, NCI, NIA, NINDS, NIMH and NIEHS). Resource sharing: We will archive, advertise and share this resource.

描述（由申请人提供）：定义为 - 在胎儿或新生儿生活的临界窗口中对挑战的反应，改变了正常发育，从而改变了对表型的持续影响，从而通过基因环境相互作用来修改表型。在啮齿动物中，妊娠（P）中产妇的营养减少（MNR）导致胎儿营养减少（FNR），这可能会因哺乳（L）的限制（l）易受肥胖症和其他慢性病而复杂化。如果较差的产后营养在FNR之后，则P中的MNR母亲会形成节俭的表型，以更好地生存。 - “预测自适应反应”。啮齿动物中的FNR，因过量（甚至是正常）的新生儿营养不匹配，也易于慢性病。在解决MNR（MNR R24）的R24中，我们在1）对照组（CTR）Baboons开发了P和L -CTR/CTR/CTR（P Diet first，l second）和2）MNR狒狒的狒狒。重量调整后的CTR（MNR/MNR）。这款R24仅在2009年6月才完成。从那以后的一年中，已经提交了11项赠款申请 - 成功完成了6份。第二个R24在2010年2月开始，在P和L（MO/MO，MO R24）中产生饮食诱发的孕产妇肥胖症（MO）的母亲喂养的母亲队列（HED）开始了2010年2月。具体目的。在胎儿和新生儿生活中暴露于养分不匹配（MM）的灵长类动物（NHP）-MNR/CTR和MNR/MO作为研究机制（MM R24）的多投资剂资源。我们致力于开发同类人群，以比较人类DP的基础机制。现在，我们有三个同伴-ctr/ctr，mnr/mnr，mo/mo。在其他六个潜在队列中，CTR/MNR，CTR/MO和MO/MNR几乎没有兴趣。我们建议开发MNR/CTR和MNR/MO的同类人群，因为正如我们所包括的几封信一样，不匹配是DP的核心 - 两个当局甚至使他们的书不匹配的权利。方法：我们控制食物摄入量，维持正常的社会和体育锻炼。最近资助的MO R24如果资助，该MM R24的同期CTR妊娠 - 节省了33％的成本。在类似表型的P狒狒期间，CTR（MNR）的70％。出生后，MNR母亲会被喂食或hed。断奶后，吃chow。 13个新信（来自圣安东尼奥以外的全部，美国以外的4个）被添加到对研究这些同胞的24个先前信件中。我们还分别提供了支持NHP工作的领先DP流行病学家的13封信。环境，研究人员和创新：PIS和SFBR为这项工作提供了独特的设施，动物和专业知识的组合。自1976年以来，PIS一直在NHLBI，NICH，NEI，NINCD，NIA NIMH，NIA NIMH，NIA NIMH，NIA NIMH，NIA NIMH，NIA NIMH，自1976年以来。广泛的MM研究存在于偏心物种上，但不是早产NHP，而关键的前自然和新生儿环境因素非常不同 - p02，霍尔糖，荷尔蒙，荷尔蒙，荷尔蒙，荷尔莫酮是非常不同的。拟议的MM R24加三个正在进行的队列为DP提供了与多个NIH机构有关的新型机会（NHLBI，NIDDK，NICHD，NICHD，NIAID，NEI，NEI，NCI，NIA，NIA，NIA，NINDS，NIMH和NIEHS）。资源共享：我们将存档，做广告并共享此资源。