Presented at the Neonatal Society 2007 Spring Meeting.
Sharkey D, Kurlak LO, Williams PJ, Stephenson T, Symonds ME, Gardner DS, Budge H
Centre for Reproduction and Early Life, University of Nottingham, NG7 2UH, UK
Introduction: Childhood obesity is increasing at an alarming rate along with other comorbidities such as hypertension and insulin resistance. The cause of this increase is multifactorial with excess energy intake and reduced exercise being major components. Monocyte Chemoattractant Protein 1 (MCP-1) plays a pivotal role in obesity, initiating inflammation in adipose and renal tissues and resulting in insulin resistance and kidney injury respectively. Surprisingly, maternal nutrient restr iction between early-to-mid gestation protects the kidney from the deleterious effects that accompany juvenile obesity but the extent to which alterations, or differential tissue regulation, occur in MCP-1 during juvenile obesity is not known. Therefore, in the present study we examined the combined effects of maternal nutritional manipulation during pregnancy and early-onset obesity on MCP-1 distribution.
Methods: Twenty six pregnant sheep were randomly assigned to a normal (7 MJ/day, n=15) or nutrient restr icted diet (NR, 3.5 MJ/day, n=11) from days 30 to 80 gestation (term = 147 days) and fed to requirements at all other times. Following weaning at 10 weeks postnatal age, offspring were either reared at pasture and remained lean (L, n=8 of normal diet) or reared in an environment of restricted activity and increased energy dense food to promote fat deposition and, thus, obesity (O, n=7 of normal maternal diet, ONR, n=11). No lean NR group were studied. All sheep were humanely euthanased at 1 year and tissues sampled. MCP-1 mRNA expression in the kidney and perirenal adipose tissue (PAT) were measured by real-time PCR, normalised to 18s rRNA and expressed as ratio of control. Statistical analyses were performed using one way analysis of variance or Kruskall-Wallis tests with post hoc comparisons to determine individual differences between groups. All animal procedures had local Animal Ethics Committee Approval and were performed in accordance with UK legislation.
Results:
Conclusion: This is the first study to demonstrate maternal nutr ient restriction, during the period of nephrogenesis, but prior to significant fat deposition in the fetus, differentially affects the inflammatory response between the kidney and adipose tissue during juvenile obesity. The role of MCP-1 is central to the mechanism of inflammation and these data suggest a potential pathway that may offer protection to those at risk of obesity related disease.
Acknowledgements: This study was supported by the British Heart Foundation.