Endocrine Abstracts

Maternal nutrient restriction predisposes the adult offspring to metabolic syndrome. We investigated the effect of energy restriction during early or late gestation on glucose-insulin dynamics during a GTT (0.5 g/kg i.v. glucose) and/or an ITT (0.75 IU/kg) prior to and after significant gain in adipose tissue. 20 sheep were either fed to maintenance (1 M; CE, n=6) or to 0.65 M during early (0–65 days, term=147days, LEE, n=7) or late (65–125 days, LEL; n=7) gestation. Lambs delivered naturally, were weaned at 12 weeks and fed at pasture to 1.5 years. At this time the first GTT and DXA scan was conducted. Thereafter all sheep gained significant weight through reduced physical activity and increased food intake. After a 10–15 kg increase in weight a second GTT, DXA and an ITT were performed. Data were analysed by univariate and RM-GLM as appropriate, with estimated marginal means presented (SPSS v14). Prenatal treatment had no effect on the first estimate of body composition or glucose-insulin metabolism (GTT) at 2years, but males were heavier (67±1 vs 52±1 kg) and fatter (17.5±1.4 vs 13.4±1.4%) than females, respectively. Weight gain (to 78±1 vs 65±1 kg, respectively) was entirely as fat since some lean mass was lost (∼2±1 kg in all groups). Increased fat mass negatively impacted glucose tolerance (AUC1_glu, 807±35 vs AUC2 _glu, 1126±45 units) and insulin sensitivity (AUC1_ins, 127±18 vs AUC2 _ins, 337±19 units) with no treatment (prenatal diet)*time interaction. There was a strong trend however (P=0.057) for an overall treatment effect on the AUC_ins (CE, 3.49±0.51; LEE, 3.70±0.49; LEL, 5.51±0.46 units), but no effect on the glucose response to the ITT. In summary, at 2 years of age in sheep, we show little ‘programmed’ defects on intermediary metabolism but rather emphasise the clear deleterious effect obesity has upon many aspects of metabolic and endocrine function.