Developmental Programming by Mismatch of Pre- and Postnatal Nutrition

描述(由申请人提供)：发育规划(DP)定义为-在胎儿或新生儿生命的关键窗口对挑战的反应，改变正常发育并由此对表型产生持续影响，通过基因-环境相互作用改变表型。在啮齿动物中，孕期母体营养素减少会导致胎儿营养素减少，这可能与限制哺乳(L)导致后代肥胖和其他慢性病有关。如果出生后营养不良，P组的母亲会发展出节俭的表型，以便更好地生存。--“预测性的适应性反应”。啮齿动物的FNR与过多(甚至正常)的新生儿营养不匹配也容易患上慢性病。在R24处理的MNR(MNR R24)中，我们从1)对照组(CTR)和L-CTR/CTR(P饲料优先，L其次)和2)MNR狒狒(MNR/MNR)的队列中培育出1)对照组(CTR)和2)MNR/CTR(饲喂70%全球体重调整的CTR)。这款R24在2009年6月才完工。自那以来的一年里，已提交了11份赠款申请，其中6份成功。第二个R24开始于2010年2月，在P和L(MO/MO，MO R24)喂养高能量饮食(HED)的母亲中开发产生膳食诱导的母亲肥胖(MO)的队列。具体目的：建立非人类灵长类(NHP)在胎儿和新生儿生活中暴露于营养不匹配(MM)的队列--MNR/CTR和MNR/MO作为研究机制的多因素资源(MM R24)。我们致力于发展队列，以比较人类DP的潜在机制。我们现在有三个队列-CTR/CTR，MNR/MNR，MO/MO。在其他六个潜在的队列中，有三个，CTR/MNR，CTR/MO和MO/MNR几乎没有兴趣。我们建议发展MNR/CTR和MNR/MO的队列，因为正如我们包括的几个字母所示，不匹配是DP的核心-两个当局甚至将他们的书命名为不匹配。方法：我们控制食物摄入量，保持正常的社交和体力活动。最近资助的MO R24为MM R24提供了同期的CTR怀孕，如果资助的话-节省了33%的成本。在发情期间，表型相似的狒狒将获得70%的CTR(MNR)。在出生后，MNR的母亲会被随意喂食，要么是食物，要么是HED。断奶后全部断奶，吃零食。在之前的24封信件中，新增了13封信件(全部来自圣安东尼奥以外的地方，4封来自美国以外的地方)，显示出人们对研究这些队列的广泛兴趣。我们还分别提供了13封来自领先的DP流行病学家的信件，支持NHP的工作。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、动物和专业知识组合。自1976年以来，PIS一直合作举办NHLBI、NICHD、NEI、NINCDS、NIA NIMH、NIDDK基金。广泛的MM研究针对的是原始物种，而不是早熟的NHP，在这些研究中，产前和新生儿的关键环境因素-P02、血糖、激素有很大不同。拟议的MM R24加上三个正在进行的队列在DP中提供了与多个NIH研究所(NHLBI、NIDDK、NICHD、NIAID、NEI、NCI、NIA、NINDS、NIMH和NIEHS)相关的新机会。资源共享：我们将对此资源进行存档、广告和共享。

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.