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NEONATAL SOCIETY ABSTRACTS

The influence of changing the macronutrient content of the maternal diet on offspring development and liver metabolism

Presented at the Neonatal Society 2009 Autumn Meeting (programme).

Almond K1, Bikker P2, Lomax M1, Symonds ME1, Mostyn A1

1 Divison of Human Development, School of Clinical Sciences, E floor East Block, University Hospital, Nottingham, UK
2 Schothorst Feed Research, Lelystad, The Netherlands

Objectives: Altering maternal nutrition affects fetal development, potentially predisposing offspring to later metabolic disease. Glucocorticoid (GC) excess has been linked to the clinical observations associated with the metabolic syndrome. Tissue sensitivity to cortisol is regulated, in part, by glucocorticoid receptor (GR) and 11-beta- hydroxysteroid-dehydrogenase (11βHSD) types 1 and 2. Several studies have shown the effects of maternal nutrient restriction on the programming of GC action in the offspring(1,2), however, dietary excess is far more characteristic of the diets consumed by a substantial number of pregnant women. The hypothesis of this study is that consuming a high-fat or protein diet during gestation decreases maternal glucose tolerance and increases offspring liver GC sensitivity potentially altering lipid metabolism.

Methods: Pregnant sows were fed one of three isoenergetic diets (Table 1), that altered only in starch, protein and fat content, between days 0 and 110 of gestation (term = 115 days). Glucose tolerance tests were carried out on day 108 of gestation in sows who received high fat and control diets. All sows delivered naturally and piglets were weighed at birth. At 7 days, one median piglet per litter were selected, humanely euthanized, a blood sample taken and its liver sampled. GR, 11βHSD-1 and 2, and peroxisome-proliferator-activated-receptor alpha (PPARα) gene expression were quantified by real-time PCR. Triglyceride (TAG) content was measured using spectrophotometric analysis following Folch extraction [3]. Plasma concentrations of glucose, non-esterified fatty acids (NEFA) and TAG were assessed using enzymatic-colorimetric assays. Offspring that were not selected for tissue sampling were raised commercially and body weight and composition was recorded at the slaughterhouse. All results were expressed as means SEM. Significant differences between groups were determined using either a T-test (parametric) or Mann-Whitney U test (non-parametric).

Results: Consuming a high fat gestational diet reduced (p<0.05) maternal glucose tolerance at term. Offspring mortality was increased (p<0.05) when mothers consumed a high fat or protein diet. Birth weight, body weight at 6 months and growth rate was unaffected by maternal diet. Offspring born to mothers receiving a high protein diet had increased (p<0.05) liver expression of GR and 11βHSD-1 at 1 week. Although not significant there was a trend towards a decrease in TAG content and increase in PPARα gene expression in the livers of offspring at 1 week of age born to mothers who consumed either the high fat or protein diets.


Table 1: Maternal diets

Conclusion: Feeding a high-fat diet reduces glucose tolerance in the mothers at term; it is unclear what effect high protein feeding has. Neonatal survival appears to be compromised when mothers consume a high-fat, or protein diet throughout gestation. Feeding a high-protein diet during pregnancy programs increased hepatic cortisol sensitivity in the newborn. Future work will further determine the effect of high-fat or protein maternal diets on offspring liver metabolism at 6 months of age.

References
1. M. G. Gnanaligham et al., Am J Phys., 289: 1407-1415, 2005
2. C. B. Whorwood et al., Endocrinology, 142(7): 2854-2864, 2001
3. J. Folch et al., Journal of Biological Chemistry, 226: 497-509, 1957

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