Proceedings of The Physiological Society

University of Manchester (2010) Proc Physiol Soc 19, C140

Oral Communications

Impact of gender on glomerular responses and inflammatory gene expression following juvenile onset obesity in sheep.

I. Bloor1, S. P. Sebert1, R. Mahajan1, M. E. Symonds1

1. Human Development, Nottingham University, Nottingham, United Kingdom.

Clinical and experimental evidence suggests that obesity mediated low grade inflammation may contribute towards organ damage and other adverse clinical effects1 that may be gender dependent. The present study aims to investigate whether obesity modifies kidney glomeruli physiology and gene expression of key regulators involved in activation of the inflammatory immune response, such as cluster of differentiation 14 (CD14)2, a lipopolysaccharide binding protein. In addition, we examined the impact of gender on these outcomes. Three months after birth, male (n=12) and female (n=10) sheep were randomly separated into two experimental groups, comprising of restricted and unrestricted activity and thus raised in either a lean (L) or obesogenic (O) environment. At ~ 17 months of age all animals were humanely euthanased and all major organs and tissues sampled. Gene expression was determined using quantitative reverse transcriptase polymerase chain reaction (RT-PCR) and expression quantified using the 2-Δct method3. Histological staining was performed using haematoxylin and eosin on paraffin-embedded renal tissue sectioned at 5μm. Glomerular area and nucleated cell count were quantified using image analysis software Volocity. Kidney weight was increased (p<0.05, student’s t-test) with obesity in males (Obese - 140.1±5.044, (n=7); Lean 120.2±7.276g, (n=5)), but not females, as was mean glomerular area (Obese - 19790±1094: lean - 14280±430.5 μm2 (p<0.05)). This adaptation was accompanied by raised mRNA abundance of CD14 with obesity in males only (Obese - 3.214±0.913: Lean - 0.992±0.168 2-Δct (p<0.01)). Our study suggests that males are much more sensitive to the adverse effects of obesity on both glomeruli physiology and inflammatory responses. The mechanisms by which females may be protected from these effects are currently being explored.

Where applicable, experiments conform with Society ethical requirements