Given their small size, high fertility and short life span, common marmosets are an efficient nonhuman primate model in which to examine the effects of early life environment on adult disease outcomes. The primary goal of the proposed research is to determine the extent to which maternal propensity to obesity or actual obesity predisposes offspring to disorders of glucose regulation and weight homeostasis in this species. These goals will be achieved through the following specific aims: 1. To establish and characterize four study populations of pregnant females that a. are made obese prior to pregnancy through exposures to a proven obesity-inducing, high-fat diet; b. have a propensity to DIO, but are maintained on the typical low fat diet during pregnancy; c. are spontaneously obese; or d. remain lean while exposed to a high fat diet. These four populations will be characterized relative to glucose metabolism and regulation, including baseline insulin and HbA1C, glucose, and response to an oral glucose tolerance test; food intake and physiological and behavioral responses to food; and body composition and circulating concentrations of leptin. 2. To characterize these study populations relative to the following variables during pregnancy and at birth: maternal glucose metabolism and regulation; maternal body composition and circulating concentrations of CRH, leptin and estradiol; placental and fetal growth and development, including placental function assessed through stereology and estimates of placental CRH, leptin and IGF production; endocrine markers of placental size and function; and infant birth weight and and circulating insulin concentration. 3. To characterize changes in body composition, feeding and metabolism from post-weaning infancy (6 months) to adulthood (24 months of age) in offspring of these pregnancies by: tracking growth trajectories while fed control or obesity-inducing diets; tracking development of feeding behaviors in weanling infants; determining response to food cues in adults; and tracking glucose metabolism and regulation. The primary null predictions are that obese females, regardless of the source of obesity will display a """"""""pre-diabetic/mild diabetic"""""""" profile resulting in fetal macrosomia and hyperinsulinemia, that the DIO propensity group may differ from the diet resistant, lean group in terms of metabolic parameters; and that adult offspring will mirror their dam in terms of body composition, feeding behavior, and glucose metabolism. ? ? ?
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