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.
(provided by applicant): MO alters OFF predisposition to chronic adult conditions - high blood pressure, diabetes and obesity. We will identify mechanisms involved to assist development of diagnostic, preventative and therapeutic strategies.
|Yang, Shanshan; Gerow, Kenneth G; Huber, Hillary F et al. (2017) A decline in female baboon hypothalamo-pituitary-adrenal axis activity anticipates aging. Aging (Albany NY) 9:1375-1385|