Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2007) 13 P166


1Dept of Molecular Endocrinology, Barts and the London Medical School, William Harvey Research Institute, Queen Mary University of London, London, United Kingdom; 2Department of Endocrine Neurobiology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary; 3Division of Endocrinology, Diabetes and Clinical Nutrition, University Hospital Basel, Basel, Switzerland; 4Department of Internal Medicine, University of Ancona, Ancona, Italy; 5Laboratory of Physiological Studies, National Institute of Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, United States.

This abstract was printed as a duplication of abstract P291 and corrected online

Background: Excess glucocorticoids result in Cushing’s syndrome (CS) which is characterised by increased food intake, central obesity, dyslipidaemia and insulin resistance, leading to the metabolic syndrome. AMPK is a regulator of energy homeostasis and plays an important role in the regulation of appetite, glucose uptake, lipogenesis and gluconeogenesis. We hypothesised that the effects of corticosteroids on metabolism would be mediated by changes in AMPK activity in a tissue-specific manner.

Methods: Rats were implanted with corticosterone-containing pellets and consumed chow and 30% sucrose for 2 weeks. Control animals were implanted with cholesterol pellets consuming sucrose or saline only. AMPK activity (kinase assay), metabolic enzyme expression (qRT-PCR) and hypothalamic endocannabinoid content were measured. Human visceral fat tissue of patients with CS was analysed for AMPK activity and compared to controls. Human ex vivo differentiated adipocytes treated with dexamethasone were also studied for AMPK activity.

Results: Corticosterone-treated rats demonstrated higher insulin, leptin, cholesterol and triglyceride levels and an increase in visceral fat weight (to 129 ±5% of controls; mean±SEM). The AMPK activity in the visceral fat of corticosterone-treated rats and CS patients was significantly lower compared to controls. The gene expression of gluconeogenic and adipogenic enzymes was increased in adipose tissue. The data on AMPK were confirmed in human adipocytes treated with dexamethasone for 24h. In the liver, fat content was increased concomitant with an increased AMPK activity. In the heart a decrease in AMPK was observed, consonant with the cardiomyopathy observed in humans. In the hypothalamus, AMPK and the endocannabinoid content were increased concordant with the increased appetite typical of CS.

Conclusion: We demonstrate that corticosteroids change AMPK activity in various tissues in a manner that may explain the increase in food intake, lipid deposition in visceral adipose and hepatic tissue and the peripheral cardiac effects of Cushing's syndrome.

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