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

• 批准号: 8147544
• 负责人: PETER W. NATHANIELSZ
• 金额: $ 53.62万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 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/8147544
• 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' 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

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. PUBLIC HEALTH RELEVANCE (provided by applicant): Poor maternal nutrition is prevalent in the USA where food is abundant postnatally. Animal studies show that mismatched fetal and neonatal nutrition predisposes offspring to chronic diseases (diabetes and obesity). There are no data from nonhuman primates to translate to humans. Data obtained will enable development of diagnostic, preventative and therapeutic strategies.

描述（由申请人提供）：发育规划（DP）定义为 - 对胎儿或新生儿生命关键窗口中挑战的反应，这些挑战改变了正常发育，从而对表型产生持久影响，通过基因-环境相互作用改变表型。在啮齿类动物中，妊娠期 (P) 母体营养减少 (MNR) 会导致胎儿营养减少 (FNR)，而哺乳限制 (L) 可能会加剧这种情况，使后代 (OFF) 容易患上肥胖和其他慢性疾病。 P 中的 MNR 母亲中的 OFF 会形成节俭的表型，以便在 FNR 后产后营养不良的情况下更好地生存。 - “预测性适应性反应”。啮齿动物的 FNR 与过量（甚至正常）的新生儿营养不匹配也容易导致慢性疾病。在解决 MNR (MNR R24) 的 R24 中，我们开发了狒狒 OFF 队列，其中包括 1) 对照 (CTR) 狒狒，在 P 和 L 中随意喂养 - CTR/CTR（P 饮食第一，L 第二）和 2) MNR 狒狒，喂养全球 70% 的狒狒权重调整后的点击率 (MNR/MNR)。 R24 于 2009 年 6 月才完成。此后的一年里，已提交 11 份资助申请，其中 6 份成功。第二个 R24 项目于 2010 年 2 月开始，旨在开发由食用高能量饮食 (HED) 的母亲组成的 OFF 队列，在 P 和 L 中产生饮食诱发的孕产妇肥胖 (MO)（MO/MO，MO R24）。 具体目标：开发非人类队列灵长类动物 (NHP) OFF 在胎儿和新生儿生命中暴露于营养不匹配 (MM) - MNR/CTR 和 MNR/MO 作为研究机制的多研究者资源 (MM R24)。我们致力于开发队列来比较人类 DP 的潜在机制。我们现在有三个队列 - CTR/CTR、MNR/MNR、MO/MO。在其他六个潜在群组中，其中三个 CTR/MNR、CTR/MO 和 MO/MNR 兴趣不大。我们建议开发 MNR/CTR 和 MNR/MO 队列，因为正如我们包含的几封字母所示，不匹配是 DP 的核心——两个权威机构甚至将他们的书命名为“不匹配”。方法：我们控制食物摄入量，维持正常的社交和身体活动。最近资助的 MO R24 如果资助的话，可以为该 MM R24 提供同期 CTR 怀孕 - 成本节省 33%。在 P 期间，类似表型的狒狒将被喂食 70% 的 CTR (MNR)。出生后，MNR 母亲可以随意喂养食物或 HED。断奶后就全部停止吃食物了。先前 24 封信件中添加了 13 封新信件（全部来自圣安东尼奥以外地区，4 封来自美国以外地区），显示出人们对研究这些群体的广泛兴趣。我们还单独提供了来自 DP 顶尖流行病学家的 13 封支持 NHP 工作的信件。环境、研究人员和创新：PI 和 SFBR 为这项工作提供了设施、动物和专业知识的独特组合。自 1976 年以来，PI 一直与 NHLBI、NICHD、NEI、NINCDS、NIA NIMH、NIDDK 合作资助。对晚熟物种存在广泛的 MM 研究，但对早成 NHP 却没有，其中关键的产前和新生儿环境因素 - P02、葡萄糖、激素非常不同。拟议的 MM R24 加上三个正在进行的队列为与多个 NIH 机构（NHLBI、NIDDK、NICHD、NIAID、NEI、NCI、NIA、NINDS、NIMH 和 NIEHS）相关的 DP 提供了新的机会。资源共享：我们将对该资源进行归档、宣传和共享。 公共卫生相关性（由申请人提供）：在产后食物丰富的美国，孕产妇营养不良的现象普遍存在。动物研究表明，胎儿和新生儿营养不匹配会使后代容易患慢性疾病（糖尿病和肥胖）。没有来自非人类灵长类动物的数据可以转化为人类。获得的数据将有助于制定诊断、预防和治疗策略。