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）：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。在针对MNR的R24（MNR R24）中，我们在1）对照组（CTR）的狒狒中开发了喂食AD Lib的狒狒（CTR）狒狒在P和L -CTR/CTR中喂养AD LIB（P Diet，First，L second）和2）MNR Baboons喂养70％全球体重调节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。 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用于研究机制的多启示剂资源（MM R24）。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，NINCDS，NIA NIMH，NIA NIMH，NIA NIMH，NIA NIMH，NIA NIMH，NIA NIMH，NIA NIMH，NIA NIMH，NIA NIMH，NIA NIMH和NIDDK的资金。对少数物种进行了广泛的MM研究，而不是早产性NHP，其中关键的前自然和新生儿环境因素 - p02，葡萄糖，葡萄糖，荷尔莫酮非常不同。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。 公共卫生相关性（由申请人提供）：在美国粮食量丰富的美国，孕产妇营养不佳。动物研究表明，不匹配的胎儿和新生儿营养使后代对慢性疾病（糖尿病和肥胖症）。没有来自非人类灵长类动物的数据来转化为人类。获得的数据将能够开发诊断，预防和治疗策略。