Presented at the Neonatal Society 2006 Widdowson Meeting (programme).
Bos PM1, Symonds ME1, McMillen IC2, Gardner DS3
1 Centre for Reproduction and Early Life, School of Human Development, University Hospital Nottingham, Nottingham, UK
2 School of Pharmacy and Medical Sciences, University of South Australia, Australia
3 Centre for Reproduction and Early Life, School of Veterinary Medicine and Science, Sutton Bonington, University of Nottingham, Nottingham, UK
Introduction: Obesity is a major health problem in our present day society. The distribution of adipose tissue has an important impact on the risk factors associated with obesity (1). In sheep visceral AT distribution changes dramatically in favour of the omental fat depot during the first months of life and remains set thereafter. In formula fed sheep the visceral fat distribution was altered in favour of the perirenal depot (2). Glucocorticoids influence regional lipogenesis, through the densities of glucocorticoid receptor (GR) and 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD-1) (3,4). This study investigated the effect of obesity and formula feeding on GR and 11β-HSD-1 in regional fat depots in sheep at one year of age.
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 group were kept with the mother throughout lactation, the OFF group received formula feeding. All animals were weaned at 8-10 weeks into a f ield (LC; unrestricted activity) or barn (OC and OFF; restricted activity). After one year each sheep was humanely euthanased and AT from omental and perirenal depots was collected. RNA was extracted and mRNA abundance for GR and 11β-HSD-1 were measured using real time PCR and normalised against 18S rRNA. Data were first analysed with REML modelling followed by appropriate parametric or nonparametric post hoc tests (Kruskal Wallis / Wilcoxon) using SPSS v14.0 for Windows. All experiments were undertaken in accordance with UK ethical guidelines.
Results: Sheep in the OC and OFF group were significantly heavier than sheep in the LC group. Sheep in the OFF group had relatively more perirenal fat compared to both other groups (47% of total visceral AT vs. 38% for LC and 37% for OC). Perirenal 11β-HSD-1 and omental GR and 11β-HSD-1 RNA was lower in the obese groups than in the LC group. The effects were more pronounced in omental tissue (Figure 1) than in perirenal tissue (Figure 2). GR and 11β-HSD-1 levels were not different between depots within groups.
Discussion: The lower GR and 11β-HSD-1 levels in the obese groups indicate a compensatory down regulation of glucocorticoid sensitivity to obesity. This effect is more pronounced in omental than in perirenal tissue, which may explain a shift towards a more perirenal fat distribution in the obese formula fed animals. A possible explanation for this tissue dependent down-regulation might be a different concentration of hexose-6-phosphate dehydrogenase, which supplies co-factor for 11β-HSD-1, in different tissues.
References
1. Després JP et al Nature 2006;444:881-887
2. Gardner DS et al Pediatric research 2005 (Abstract);58(5):1028
3. Seckl JR et al Recent Prog Horm Res 2004;59:359-393
4. Gnanalingham MG et al Am J Physiol Regul Integr Comp Physiol 2005;289:R1407-1415
Fig 1: Relative omental 11β-HSD-1 expression Fig 2: Relative perirenal 11β-HSD-1 expression