9.6 DIFFERENTIAL EFFECTS OF MATERNAL NUTRIENT RESTRICTION ON INFLAMMATION IN RENAL AND ADIPOSE TISSUE IN OBESE JUVENILE OFFSPRING: THE ROLE OF TLR4 AND CCR2

D. Sharkey, P. Williams, P. Bos, S. Sebert, D. Gardner, M. Symonds, H. Budge. University of Nottingham, Nottingham, UK

Introduction: Obesity is associated with a chronic inflammatory state. Key proinflammatory genes involved include Toll-like receptor 4 (TLR4) and chemokine receptor 2 (CCR2). We have previously shown, in sheep, that early-to-mid maternal nutrient restriction protects the kidney from the deleterious effects of juvenile obesity. The extent to which alterations, or differential tissue regulation, occur in these key genes after adolescent onset obesity is unknown. We examined the combined effects of maternal nutrient restriction during pregnancy and early-onset obesity on their distribution.

Methods: Eighteen pregnant sheep were randomly assigned to a normal (C, 7 MJ/day, n  =  8) or nutrient restricted diet (NR, 3.5 MJ/day, n  =  10) from days 30 to 80 gestation (term 147 days). After weaning, offspring had restricted activity and increased energy-dense food to promote obesity. Sheep were humanely killed at 1 year and tissues sampled. mRNA abundance of genes of interest in renal and perirenal adipose tissue were measured by real-time PCR. Animal ethics committee approval was given.

Results: Birthweight and weight at 1 year were not different between groups. Both TLR4 (C 1.0 ± 0.2, NR 2.0 ± 0.3, p<0.05) and CCR2 (C 1.0 ± 0.2, NR 3.9 ± 1.1, p<0.05) were upregulated in perirenal adipose tissue of nutrient restricted offspring but downregulated in the kidney (C 1.0 ± 0.2, NR 0.6 ± 0.1, p<0.05, C 1.0 ± 0.2, NR 0.4 ± 0.1, p<0.05, respectively).

Conclusions: Maternal nutrient restriction adversely affects adipose tissue through key proinflammatory genes but conversely protects the kidney from such effects. Identifying the mechanisms may offer potential tissue-specific therapies aimed at reducing the burden of the metabolic syndrome.

Funding: Funded by the British Heart Foundation

9.7 THE EFFECT OF CAESAREAN SECTION AND A SINGLE ENTERAL FEED ON LIVER METABOLISM IN RESPONSE TO TOTAL PARENTERAL NUTRITION

M. J. Hyde¹, J. L. …