Glucose homeostasis and metabolic adaptation in the pregnant and lactating sheep are affected by the level of nutrition previously provided during her late fetal life.

This study investigated whether undernutrition (UN) during late fetal life can programme the subsequent adult life adaptation of glucose homeostasis and metabolism during pregnancy and lactation. Twenty-four primiparous experimental ewes were used. Twelve had been exposed to a prenatal NORM level of nutrition (maternal diet approximately 15 MJME/d) and 12 to a LOW level of nutrition (maternal diet approximately 7 MJME/d) during the last 6 weeks pre-partum. The experimental ewes were subjected to two intravenous glucose tolerance tests (IGTT) in late gestation (one prior to (G-IGTT) and one by the end of a feed restriction period (RG-IGTT)), and a third around peak lactation (L-IGTT). LOW had lower basal insulin concentrations during lactation, and significantly decreased absolute insulin secretion during the L-IGTT in spite of similar glucose tolerance, indicating increased insulin sensitivity in LOW during lactation. There was no effect of prenatal UN on glucose tolerance during G-IGTT, however, during RG-IGTT LOW was more glucose intolerant and apparently more insulin resistant compared to NORM. In conclusion, UN during late fetal life in sheep impairs subsequent pancreatic insulin secretory capacity during adult life, and reduces plasticity of down-regulation of insulin secretion in response to a metabolic challenge. Furthermore, prenatal UN appears to programme mechanisms, which in young adult females can shift the insulin hypersensitivity observed during early lactation into an insulin resistance observed during late gestation and feed restriction. Early postnatal UN caused by lowered milk intake in early postnatal life may have contributed to these phenomena.

Late foetal life nutrient restriction and sire genotype affect postnatal performance of lambs.

This experiment investigates the effects of maternal nutrient restriction in late gestation on the offsprings' postnatal metabolism and performance. Forty purebred Shropshire twin lambs born to ewes fed either a high-nutrition diet (H) (according to standard) or a low-nutrition (L) diet (50% during the last 6 weeks of gestation) were studied from birth until 145 days of age. In each feeding group, two different sires were represented, 'growth' (G) and 'meat' (M), having different breeding indices for the lean : fat ratio. Post partum all ewes were fed the same diet. Lambs born to L-ewes had significantly lower birth weights and pre-weaning growth rates. This was especially pronounced in L-lambs born to the M-ram, which also had markedly lower pre-weaning glucose concentrations than the other three groups of lambs. L-lambs converted milk to live weight with an increased efficiency in week 3 of life. Their glucose concentrations and growth rates were both increased. Plasma glucose concentrations in LM-lambs became similar to those observed in H-lambs post-weaning. However, LM-lambs continued to be lighter than the other groups throughout the experimental period and were unable to compensate for the reduced weight at birth despite having the highest daily fractional growth rates. LG-lambs had the highest plasma glucose concentrations of all four groups of lambs, and they indeed reached body weights comparable to those of the H-lambs by 145 days of age. The increased growth rate post-weaning in L-lambs was not reflected in fat deposition, as L-lambs had lower fat deposition than H-lambs. This may relate to the lower plasma insulin levels found in the L-lambs than in the H-lambs. In conclusion, a 50% reduction of maternal nutrient supply in the last 6 weeks of gestation reduces the birth weight and pre-weaning growth of the offspring due to lower milk intake. Growth rates can be restored when an adequate post-weaning diet is provided, but the prenatal nutrition may programme postnatal metabolism differentially depending on genotype, thus affecting the ability of the ad libitum-fed lamb to achieve a given body weight by a certain age.

Effects of twinning and periconceptional undernutrition on late-gestation hypothalamic-pituitary-adrenal axis function in ovine pregnancy.

The relationships between reduced size at birth, increased activity of the hypothalamic-pituitary-adrenal (HPA) axis, and increased risk of disease in adulthood are well described in singletons but are much less clear in twins. This may be because the physiological processes underlying reduced size at birth are different in singletons and twins. Periconceptional undernutrition can cause altered activity of the fetal and postnatal HPA axis without altering size at birth. However, the independent effects of periconceptional undernutrition and twinning on activity of the maternal and fetal HPA axes are not well described. We therefore studied maternal and fetal HPA axis function during late gestation in twin and singleton sheep pregnancies, either undernourished around conception or fed ad libitum. We found that twinning led to suppressed baseline HPA axis function and decreased adrenal sensitivity to ACTH stimulation but increased fetal pituitary ACTH response both to direct stimulation by CRH (ACTH area under the curve response: 29.7 +/- 2.2 vs. 17.1 +/- 1.6 ng/min x ml, P < 0.01) and to decreased cortisol negative feedback. In contrast, periconceptional undernutrition resulted in a decreased pituitary response (ACTH area under the curve response: 19.4 +/- 1.6 vs. 26.1 +/- 2.2 ng/min x ml, P = 0.02) but no difference in adrenal response. Thus, the HPA axis function of twin sheep fetuses in late gestation is very different from that of control and undernourished singletons. If the HPA axis is an important mediator between fetal adaptations and adult disease, these data may help explain why the relationship between fetal growth and postnatal physiology and disease risk is inconsistent in twins.

Programming of intermediate metabolism in young lambs affected by late gestational maternal undernourishment.

Effects of moderate maternal undernourishment during late gestation on the intermediary metabolism and maturational changes in young lambs were investigated. 20 twin-bearing sheep, bred to two different rams, were randomly allocated the last 6 wk of gestation to either a NORM diet [barley, protein supplement, and silage ad libitum approximately 15 MJ metabolizable energy (ME)/day] or a LOW diet (50% of ME intake in NORM, offered exclusively as silage approximately 7 MJ ME/day). Post partum, ewes were fed to requirement. After weaning, lambs were fed concentrate and hay ad libitum. At 10 and 19 wk of age, lambs were subjected to an intravenous glucose tolerance test (IGTT) followed by 24 h of fasting. Heat energy (HE) was determined in a respiration chamber at 9 or 20 wk of age. LOW lambs had a lower birth weight and continued to be lighter throughout the experiment. Glucose tolerance did not differ between groups. However, 19-wk-old LOW lambs secreted less insulin during IGTT, released more NEFA, and tended to have lower leptin during fasting than NORM. Surprisingly, several metabolite and hormone responses during IGTT and fasting were greatly influenced by the paternal heritage. In conclusion, when lambs entered adolescence (19 wk) programming effects of late prenatal malnutrition on the glucose-insulin homeostasis and metabolism were manifested: LOW lambs had less insulin-secretory capacity, but this was apparently compensated for by increased target tissue sensitivity for insulin, and adipose lipolytic capacity increased during fasting. Thereby, glucose may be spared through increased lipid oxidation, but overall energetic efficiency is apparently deteriorated rather than improved.