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，发育期间的母体肥胖（MO）会改变后代（OFF）的身体组成，易患慢性成人疾病（心脏病、肥胖症、抑郁症、糖尿病）。令人信服的，控制啮齿动物的研究比比皆是，但发表的非人灵长类动物（NHP）的数据关闭结果的MO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量，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，随机选择的相似表型的雌性动物将保持对照（CTR）自由饮食或高脂肪、高碳水化合物、高适口性饮食（HPD），我们开发了这种饮食以在年轻的未经产雌性动物中产生肥胖。MO女性在怀孕和哺乳期保持这些饮食。断乳时吃CTR饲料。将男性和女性OFF群组表征至3岁。首席研究员自1976年以来一直由NIH资助进行假设驱动研究。非妊娠动物的初步数据是在近100，000美元的机构支持下获得的。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人员来解决。创新：迄今为止，只有一个其他小组研究MO对NHP OFF的影响。他们的模型在许多方面都不同，包括个人的食物摄入记录和研究的怀孕一致性。工作环境：在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关闭之前，期间和之后怀孕。我们已经收到NHLBI，NICHD，NEI，NINCDS，NIA，NIMH，NIDDK和NSF资助NHP研究，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，并包括来自24名研究人员的信件，他们希望研究这些关闭。我们也将广泛宣传这一资源。重要性：这项耗资50亿美元的国家儿童研究将跟踪10万名18岁以下的妇女。在人类怀孕期间，很难获得评估发育规划的关键信息。NHP研究允许营养干预，重复活检，母亲和OFF的血液和身体测量。狒狒比人类成熟得更快，可以提供及时的数据来指导NCS。充分表征的CTR和接受HPD的肥胖经产母亲将从出生到老年分娩OFF用于研究。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者共享。与其他NHP相比，狒狒具有独特的优势-单个胎儿，胎盘类似于人类，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.