The role of ghrelin in a chronic corticosterone model of obesity

Rebecca Hay (2015)R.E. Hay, M. Smorenburg, T. Rodrigues, A. Edwards, M. Klein, L. Hyland, H. MacKay, I. Karatosoreos, M. Hill, A. Abizaid

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Continuous exposure to glucocorticoids is associated with the development of obesity and metabolic syndrome. The mechanisms with which chronic exposure to glucocorticoids mediate weight gain are not well understood. Ghrelin is an orexigenic peptide hormone secreted in the gut that is involved in stress, modulating weight gain and appetite. Circulating ghrelin levels increase with stress, presenting a potential mechanism in which glucocorticoids mediate the development of obesity through the activity of ghrelin. We hypothesized that the obesogenic effects of a chronic corticosterone (CORT) treatment would be regulated by the presence of ghrelin. To test this, we exposed mice to either 1% EtOH in water or corticosterone (100µg/ml) mixed in this solution for a period of 28 days. Half of these mice also received chronic infusions of the growth hormone secretagogue receptor (GHSR) antagonist JMV2959 (100µg/day), while the other half received vehicle. Results show that animals placed on chronic CORT treatment had significantly higher (p < 0.05) body weight, food intake, and water intake compared to control animals, and this effect tended to be attenuated by treatment with the GHSR antagonist although this effect was not statistically significant. CORT treatment led to hyperleptinemia, an effect that was significantly attenuated by co-treatment with the GHSR antagonist. Plasma ghrelin levels were attenuated, whereas glucose levels were significantly higher in CORT treated animals compared to controls and regardless of whether they received the GHSR antagonist or not. These data suggest that ghrelin mediates some endocrine changes associated with the chronic corticosteroid model of obesity.