SFEBES2016 Poster Presentations Obesity and Metabolism (26 abstracts)
Glucocorticoid treatment rapidly increases AgRP and food intake with delayed effects on other metabolic systems
Erika Harno 1 , Alison Davies 1 , Tiffany-Jayne Allen 1 , Charlotte Sefton 1 , Jonathan R Wray 1 , Thanuja Gali Ramamoorthy 1 , Anthony P Coll 2 & Anne White 1
1University of Manchester, Manchester, UK; 2University of Cambridge, Cambridge, UK.
Glucocorticoids are widely prescribed therapeutic agents, however long term treatment can cause increased morbidity from adverse metabolic events, including weight gain and hyperglycaemia. The mechanisms and site of action which underpin these side-effects are not fully understood. The aim of this study was to characterise phenotypic, biochemical and neurohormonal responses in mice administered corticosterone, with a particular focus on changes seen in the early stages of chronic treatment.
In 12 week old male mice given corticosterone (CORT, 75 μg/ml)-supplemented drinking water, food intake was increased after 24 h and remained elevated over 3 weeks. This was accompanied by immediate and persistent increases in the orexigenic neuropeptide Agrp, without any consistent changes in other hypothalamic factors associated with energy balance. This model caused an increase in body weight after 14 days and increased white adipose tissue (WAT) after 3 weeks. In brown adipose tissue, expression levels of genes involved in thermogenesis (Ucp-1, Ppargc1a, Cidea and Prdm16) were unchanged at day 2. However, after chronic CORT treatment, expression of all four genes was decreased, indicative of reduced energy expenditure. CORT treatment also increased circulating insulin 5-fold at 24 h but levels increased 35-fold compared to vehicle treated mice at 3 weeks. Irs-1 expression decreased after 2 days, only in skeletal muscle, but was also decreased in liver and WAT at 3 weeks, suggestive of widespread insulin resistance. Chronic CORT also caused hyperglycaemia accompanied by increased hepatic gluconeogenic genes, which was not present at 2 days.
In summary, CORT induces a sustained increase in food intake, with persistent increases in Agrp. However with chronic glucocorticoid treatment, a more widespread pattern of adverse metabolic sequelae emerge. Understanding these mechanisms may help in the design of therapeutic strategies to counteract the side-effects.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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