Developmental Programming, Maternal Obesity and Overnutrition

描述(申请人提供)：广泛的人类流行病学数据表明，母体肥胖(MO)在发育过程中改变了后代(外)的身体组成，容易患上慢性成人疾病(心脏病、肥胖症、抑郁症、糖尿病)。令人信服的、受控制的啮齿动物研究比比皆是，但发表的关于MO的非人类灵长类(NHP)结果的数据是不可用的。方法：我们建立了一个独特的系统，在保持正常的群体社交和体力活动的同时，监测和控制个体狒狒的食物摄入量。从怀孕前九个月开始，随机选择表型相似的女性，将维持对照(CTR)临时饮食或我们开发的高脂肪、高碳水化合物、高度适口的饮食(HPD)，以产生年轻的未分娩女性的肥胖。在怀孕和哺乳期间，莫母鱼会继续吃这些食物。断奶时吃CTR日粮。男性和女性非队列的特征是3岁。自1976年以来，首席研究员一直由美国国立卫生研究院资助进行假设驱动的研究。获得了关于非怀孕动物的初步数据，机构支助接近100,000美元。我们提供了研究的例子，这些研究可以由我们自己和其他提供信件的调查人员解决。创新：到目前为止，只有一个小组研究了MO对NHP关闭的影响。他们的模型在许多方面都不同，包括所研究的个体食物摄入量记录和怀孕一致性。环境：与西南国家灵长类中心合作，我们拥有所有必要的专业知识来调查雌性狒狒以及怀孕前、怀孕期间和怀孕后的情况。我们已经收到了NHLBI、NICHD、NEI、NINCDS、NIA、NIMH、NIDDK和NSF用于NHP研究的资金，并有广泛的合作。我们已经建立了一个经验丰富的外部咨询委员会，并包括24名希望研究这些问题的调查人员的来信。我们还将广泛宣传这一资源。意义：这项耗资50亿美元的国家儿童研究将跟踪调查10万名18岁以下的女性。在人类怀孕期间，很难获得评估发育规划的关键信息。NHP研究允许进行营养干预、重复活组织检查、对母亲和产后进行血液和身体测量。狒狒比人类成熟得更快，并能提供及时的数据来指导NCS。特征良好的CTR和肥胖的初产母亲在HPD上将从出生到老年送去学习。该资源将与NHLBI、NIDDK、NICHD、NIAID、NEI、NCI、NIA、NINCDS、NIMH、NIEHS等相关研究的其他研究人员共享。与其他NHP相比，狒狒具有独特的优势--单个胎儿、类似于人类的胎盘、基因阵列平台交叉反应、建立的慢性非麻醉性研究系统。

DESCRIPTION (provided by applicant): Extensive human epidemiological data show that maternal obesity (MO) during development alters offspring (OFF) body composition, predisposing to chronic adult disease (heart disease, obesity, depression, diabetes). Compelling, controlled rodent studies abound but published nonhuman primate (NHP) data on OFF outcomes of MO are unavailable. Approach: We built a unique system to monitor and control individual baboon food intake while maintaining normal group social and physical activity. From nine months before pregnancy randomly selected females of similar phenotype will be maintained either on control (CTR) ad lib diet or a high fat, high carbohydrate, highly palatable diet (HPD) which we developed to produce obesity in young, nulliparous females. MO Females stay on these diets in pregnancy and lactation. OFF eat CTR diet when weaned. Male and female OFF cohorts are characterized to age 3. The Principal Investigator's have been continuously funded by NIH since 1976 for hypothesis driven studies. Preliminary data presented on non-pregnant animals was obtained with Institutional support approaching $100,000. We present examples of studies that can be addressed by ourselves and other investigators who have provided letters. Innovation: To date only one other group studies MO effects on NHP OFF. Their model differs in many ways including individual food intake records and uniformity of pregnancy studied. Environment: In collaboration with the Southwest National Primate Center we have all expertise necessary to investigate female baboons and OFF before, during and after pregnancy. We have received NHLBI, NICHD, NEI, NINCDS, NIA, NIMH, NIDDK and NSF funding for NHP studies and have extensive collaborations. We have established an experienced External Advisory Committee and include letters from 24 investigators who would like to study these OFF. We will also advertise this resource widely. Significance: The $5 billion National Children's Study will follow OFF of 100,000 women to age 18 yrs. Critical information to evaluate developmental programming is difficult to obtain in human pregnancy. NHP studies permit nutritional interventions, repeated biopsies, blood and body measurements of mothers and OFF. Baboons mature faster than humans and can provide timely data to guide the NCS. Well-characterized CTR and obese primiparous mothers on a HPD will deliver OFF for study from birth to old age. This resource will be shared with other investigators in studies relevant to NHLBI, NIDDK, NICHD, NIAID, NEI, NCI, NIA, NINCDS, NIMH, NIEHS and others. The baboon has unique strengths compared to other NHP - single fetus, placenta resembling the human, gene array platform cross- reactivity, established systems for chronic unanaesthetized studies.