Endocrine Abstracts (2004) 7 OC35

Continuous subcutaneous administration of ghrelin results in accumulation of adipose tissue, independent of hyperphagia or body weight gain

AM Wren1, CJ Small1, EL Thomas2, CR Abbott1, MA Ghatei1, JD Bell2 & SR Bloom1

1Department of Metabolic Medicine, Faculty of Medicine, Imperial College London, UK; 2Robert Steiner MR Unit, MRC Clinical Sciences Centre, Imperial College London, UK.

Ghrelin, a circulating gastric hormone, stimulates food intake in rodents and humans and hyperphagia, weight gain and adiposity on chronic administration in rodents. Here we investigated the effect of chronic subcutaneous ghrelin on fat volume and distribution using magnetic resonance imaging (MRI). Male Wistar rats were implanted with subcutaneous osmotic mini-pumps delivering saline (S, n=10) or ghrelin 30nmol/24hours (n=18). In order to investigate the hyperphagia-independent effects of ghrelin, a group of ghrelin-treated rats (ghrelin pair-fed, GPF, n=8) were pair fed to the amount eaten by the saline controls whilst another group (G, n=10) were freely fed. Food intake and body weight were measured daily for seven days. Animals were then killed and MRI was performed on a randomly selected subgroup from each treatment allocation (G n=6, GPF n=5, S n=5) to estimate adipose tissue volume. Ghrelin-treated rats were hyperphagic (cumulative 7-day food intake G 192.8 plus/minus 5.5g vs S 169.8 plus/minus 3.9g, p<0.01) and gained more weight (54.6 plus/minus 3.8g, p<0.001) than saline-treated (32.0 plus/minus 2.3g) or GPF rats (33.6 plus/minus 1.5g). However, both ghrelin-treated groups had increased adipose tissue volume compared to saline-treated controls. Freely-fed ghrelin treated rats had significantly increased total (G 39.3 plus/minus 2.5ml/rat vs S 31.2 plus/minus 1.8ml/rat) and visceral (G 13.6 plus/minus 1.3ml/rat vs S 9.7 plus/minus 0.7ml/rat) adipose tissue volume (p<0.05) with a trend towards increased subcutaneous adipose tissue volume (G 25.7 plus/minus 1.6ml/rat vs S 21.5 plus/minus 1.2ml/rat) whilst ghrelin pair-fed rats had significantly increased visceral adipose tissue volume (12.7 plus/minus 0.7ml/rat, p<0.05 vs S) with a trend towards increased total (37.2 plus/minus 2.1ml/rat) and subcutaneous (24.4 plus/minus 1.5ml/rat) adipose tissue volume. These differences were unaltered by correction for total body weight. Thus ghrelin appears to favour adipose tissue deposition independently from its effect on food intake.

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