Developmental Programming, Maternal Obesity and Overnutrition

描述（由申请人提供）：大量的人类流行病学数据表明，发育期间的母亲肥胖（MO）会改变后代（OFF）的身体组成，易患成人慢性疾病（心脏病、肥胖症、抑郁症、糖尿病）。令人信服的对照啮齿类动物研究大量存在，但发表的非人类灵长类动物（NHP）关于MO的OFF结果的数据不可用。方法：我们建立了一个独特的系统来监测和控制狒狒个体的食物摄入，同时保持正常的群体社交和身体活动。从怀孕前9个月开始，我们将随机选择具有相似表型的雌性小鼠进行控制（CTR）随意饮食或高脂肪、高碳水化合物、高美味饮食（HPD），我们开发了高脂肪、高碳水化合物、高美味饮食（HPD），以使未生育的年轻雌性小鼠肥胖。雌性在怀孕和哺乳期间保持这些饮食。断奶后吃CTR饮食。男性和女性OFF队列的特征为3岁。自1976年以来，美国国立卫生研究院一直资助首席研究员进行假设驱动的研究。在接近10万美元的机构支持下，获得了有关未怀孕动物的初步数据。我们提出了一些研究的例子，这些研究可以由我们自己和其他提供信件的研究者来解决。创新：迄今为止，只有另外一个小组研究MO对NHP OFF的影响。他们的模型在很多方面都有所不同，包括个人的食物摄入记录和怀孕研究的一致性。环境：与西南国家灵长类动物中心合作，我们拥有所有必要的专业知识来调查雌性狒狒和OFF在怀孕前，怀孕期间和怀孕后的情况。我们已经获得了NHLBI， NICHD， NEI， NINCDS， NIA， NIMH， NIDDK和NSF的NHP研究资助，并有广泛的合作。我们已经成立了一个经验丰富的外部咨询委员会，其中包括24名调查员的来信，他们希望研究这些OFF。我们也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对10万名18岁的女性进行跟踪调查。评估发育规划的关键信息很难在人类妊娠中获得。NHP研究允许营养干预，反复活检，血液和身体测量母亲和OFF。狒狒比人类成熟得更快，可以提供及时的数据来指导NCS。具有良好特征的CTR和HPD上肥胖的初产母亲将从出生到老年进行研究。此资源将与其他研究人员在与NHLBI、NIDDK、NICHD、NIAID、NEI、NCI、NIA、NINCDS、NIMH、NIEHS等相关的研究中共享。与其他NHP相比，狒狒具有独特的优势-单胎，类似人类的胎盘，基因阵列平台交叉反应性，建立了慢性非麻醉研究系统。

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.