Exposure to a high fructose diet during pregnancy remodels the intestinal and body composition in the near-term pregnant offspring

Obesity – A Physiological Perspective (Newcastle, UK) (2014) Proc Physiol Soc 32, PC024

Poster Communications: Exposure to a high fructose diet during pregnancy remodels the intestinal and body composition in the near-term pregnant offspring

S. Astbury1,2, A. Song2, B. Nielsen2, N. Coursen2, A. Dunichand-Hoedl2, R. Bell2

1. Child Health, Obstetrics and Gynaecology, University of Nottingham, Nottingham, United Kingdom. 2. Human Nutrition, University of Alberta, Edmonton, Alberta, Canada.

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Background and aims: Excess caloric load or a proinflammatory diet may contribute to gut barrier dysfunction, leading to increased nutrient uptake and components of the microbiota passing into the systemic circulation. These effects have been linked to the development of obesity and the metabolic syndrome1,2. Maternal diet and diabetes in pregnancy have been shown to adversely affect many aspects of offspring development. This study examined the effect of a high fructose diet during gestation on gut permeability in female, pregnant offspring.Methods: Female Wistar rats were placed on either 10% fructose (f) or distilled water (c) at 8 weeks of age and were mated at 10 weeks, with diet continuing through gestation. The offspring were then maintained on the same diet as their dams (c, n=10 and f, n=10) starting from 1 week post-weaning. The offspring were then mated at 10 weeks of age, with tissue collected at gestational day 20 (GD20). Their body composition was determined by MRI directly prior to euthanasia. Ileum and jejunum sections were taken from the small intestine and snap-frozen followed by total RNA extraction for quantitative PCR. Four epithelial tight junction genes were used as markers of intestinal permeability: claudin-3 (CLDN-3), occludin (OCLN), junctional adhesion molecule A (JAMA) and zonulin-1 (ZO-1). Gene expression was measured relative to GAPDH and RPLP0. Groups were compared using t-test or Mann-Whitney U test as appropriate. All values are mean±SEM.Results: Birth weight was significantly reduced in the f group (c=4.23g±0.5 vs f=3.94g±0.8,p<0.05). Adult weights were unaffected but lean mass reduced and fat mass raised (% lean c=75.8±0.3 vs f=71.4±1.0, p<0.05 and % fat c=11.4%±0.5 vs f=16.8%±1.3, p<0.01). Gut length was also reduced in the f group (c=128.5cm±1.8 vs f=123.8cm±0.4, p<0.05) and was accompanied with reduced gene expression (p<0.05) for JAMA (0.62±0.06), OCLN (0.44±0.08) and ZO-1 (0.39±0.05) in the jejunum, but not the ileum. Conclusion: A high-fructose diet during pregnancy may adversely affect gut development in the offspring via a decrease in the expression of genes coding for a number of epithelial tight junction proteins. This response appears to be confined to the jejunum and may contribute to an increase in energy uptake across the gut, thereby leading to an increase in fat mass at the expense of skeletal muscle.



Where applicable, experiments conform with Society ethical requirements.

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