The goal of the proposed research is to characterize dietary and endocrine factors in early gestational undernutrition which are relevant to the organization of body weight regulatory capabilities. Our previous work has shown that if pregnant rats are food restricted to 50% of prepregnancy intake levels for the first two trimesters of pregnancy and then refed ad libitum, then male offspring of these rats will subsequently become obese. In the first experiment of this early period of undernutrition by systematically varying the point of onset of undernutrition throughout the gestational period. Optimizing temporal aspects of this undernutrition, and thereby maximizing the relevant metabolic consequences will substantially aid our subsequent investigations of metabolic factors in the etiology of this form of obesity. In the second experiment we will be assessing the impact of gestational undernutrition/refeeding and third trimester insulin injections, on maternal and fetal insulin and glucose levels. For reasons described in the proposal we feel that maternal/fetal insulin levels in the third trimester may be crucial to the subsequent development of offspring obesity. In the third experiment we will assess the impact of gestational undernutrition.refeeding and third trimester insulin injections on subsequent adult offspring glucose and insulin tolerance in response to oral and jugular glucose loads. The model that we are testing (Dorner, 1974) would argue that these responses should be exaggerated under both experimental conditions and that this exaggerated response contributes to the observed obesity. In the final experiment we will assess the impact of gestational undernutrition/refeeding and third trimester insulin injections on the subsequent responsiveness of offspring norepinephrine systems in hypothalamic areas relevant to the control of food intake and body weight. This is a preliminary attempt to establish a neural basis for our observed organizational effects.
| Jones, A P; Olster, D H; States, B (1996) Maternal insulin manipulations in rats organize body weight and noradrenergic innervation of the hypothalamus in gonadally intact male offspring. Brain Res Dev Brain Res 97:16-21 |
| Jones, A P; Pothos, E N; Rada, P et al. (1995) Maternal hormonal manipulations in rats cause obesity and increase medial hypothalamic norepinephrine release in male offspring. Brain Res Dev Brain Res 88:127-31 |
