Proceedings of The Physiological Society
University of Edinburgh (2007) Proc Physiol Soc 6, C8
Influence of glucocorticoids on nutritional manipulation of regional adipose tissue distribution
P. M. Bos1, M. E. Symonds1, I. C. McMillen2, D. S. Gardner1
1. Centre for Reproduction and Early Life, University of Nottingham, Nottingham, Nottinghamshire, United Kingdom. 2. School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA, Australia.
Introduction Glucocorticoids (GCs) have an important role in adipogenesis (1). The effects of GCs are mediated by the enzymes 11β-hydroxysteroid dehydrogenase type 1 and 2 (11βHSD1 and -2). 11βHSD1 activates cortisone into cortisol while 11βHSD2 has an opposite effect. The action of GCs is also dependent on the abundance of the glucocorticoid receptor (GR). In sheep the distribution of visceral adipose tissue changes dramatically from mainly perirenal to mainly omental fat in the first 6 months of life. In animals which were formula fed in the first 3 months of life this change is less pronounced (2). The aim of this study was to investigate the influence of GCs on these changes in fat distribution and the nutritional regulation of this effect. Methods Twenty-three sheep offspring were randomly allocated to either a lean control (LC, n=8), obese control (OC, n=7) or obese formula fed (OFF, n=8) group. The LC and OC groups were kept with the mother throughout lactation, the OFF group received formula feeding. All animals were weaned at 8-10 weeks into a field (LC; unrestricted activity) or barn (OC and OFF; restricted activity). After one year each sheep was humanely euthanased and adipose tissue from omental, perirenal and subcutaneous depots was collected. RNA was extracted and mRNA abundance for GR, 11βHSD1 and 11βHSD2 was measured using real time PCR and normalised against 18S rRNA. Data were first analysed with REML modelling followed by appropriate parametric or non-parametric post hoc tests (ANOVA / Kruskal Wallis) using SPSS v14.0 for Windows. A significance level of p = 0.0166 was used in all post hoc test. Results Sheep in the OC and OFF group were significantly heavier than sheep in the LC group. The regional deposition of visceral fat was different in the OFF group compared to the other groups (48±2% omental and 47±2% perirenal fat in OFF vs. 58±3% and 36±3% respectively in LC sheep). Both GR and 11βHSD1, but not 11βHSD2, were affected by a combination of nutritional group and fat region. In the omental region the GR expression was higher in the LC group compared to the OC and OFF groups (p=0.007 LC vs. OC and p<0.001 LC vs. OFF, figure 1). In the perirenal region there was no difference between groups and in the subcutaneous region the LC and OC group were increased compared to the OFF group (p<0.001 LC vs. OFF and p=0.002 OC vs. OFF, figure 2). 11βHSD1 mRNA abundance was higher in the LC group compared to the OC and OFF groups in the omental (p=0.001 LC vs. OC and p=0.001 LC vs. OFF) and perirenal region (p=0.015 LC vs. OC and p=0.012 LC vs. OFF). In the subcutaneous region the LC group was only increased compared to the OFF group (p=0.015). Discussion The relatively decreased omental fat mass in obese formula fed sheep is paralleled by decreased GR and 11βHSD1 expression, indicating nutritional regulation of adiposity in early life.Reference 1 : Gnanalingham MG et al. Am J Physiol Regul Integr Comp Physiol 2005;289:R1407-1415Reference 2 : Gardner DS et al. Pediatric research 2005 (Abstract);58(5):1028
Where applicable, experiments conform with Society ethical requirements