AMP-activated protein kinase mediates glucocorticoid-induced metabolic changes : a novel mechanism in Cushing's syndrome
JournalArticle (Originalarbeit in einer wissenschaftlichen Zeitschrift)
 
ID 1196445
Author(s) Christ-Crain, M.; Kola, B.; Lolli, F.; Fekete, C.; Seboek, D.; Wittmann, G.; Feltrin, D.; Igreja, S. C.; Ajodha, S.; Harvey-White, J.; Kunos, G.; Müller, B.; Pralong, F.; Aubert, G.; Arnaldi, G.; Giacchetti, G.; Boscaro, M.; Grossman, A. B.; Korbonits, M.
Author(s) at UniBasel Christ-Crain, Mirjam
Müller, Beat
Year 2008
Title AMP-activated protein kinase mediates glucocorticoid-induced metabolic changes : a novel mechanism in Cushing's syndrome
Journal FASEB Journal
Volume 22
Number 6
Pages / Article-Number 1672-83
Keywords obesity, insulin resistance, lipid metabolism
Abstract Chronic exposure to glucocorticoid hormones, resulting from either drug treatment or Cushing's syndrome, results in insulin resistance, central obesity, and symptoms similar to the metabolic syndrome. We hypothesized that the major metabolic effects of corticosteroids are mediated by changes in the key metabolic enzyme adenosine monophosphate-activated protein kinase (AMPK) activity. Activation of AMPK is known to stimulate appetite in the hypothalamus and stimulate catabolic processes in the periphery. We assessed AMPK activity and the expression of several metabolic enzymes in the hypothalamus, liver, adipose tissue, and heart of a rat glucocorticoid-excess model as well as in in vitro studies using primary human adipose and primary rat hypothalamic cell cultures, and a human hepatoma cell line treated with dexamethasone and metformin. Glucocorticoid treatment inhibited AMPK activity in rat adipose tissue and heart, while stimulating it in the liver and hypothalamus. Similar data were observed in vitro in the primary adipose and hypothalamic cells and in the liver cell line. Metformin, a known AMPK regulator, prevented the corticosteroid-induced effects on AMPK in human adipocytes and rat hypothalamic neurons. Our data suggest that glucocorticoid-induced changes in AMPK constitute a novel mechanism that could explain the increase in appetite, the deposition of lipids in visceral adipose and hepatic tissue, as well as the cardiac changes that are all characteristic of glucocorticoid excess. Our data suggest that metformin treatment could be effective in preventing the metabolic complications of chronic glucocorticoid excess.
Publisher Federation of American Society of Experimental Biology
ISSN/ISBN 0892-6638 ; 1530-6860
edoc-URL http://edoc.unibas.ch/dok/A6006614
Full Text on edoc No
Digital Object Identifier DOI 10.1096/fj.07-094144
PubMed ID http://www.ncbi.nlm.nih.gov/pubmed/18198220
ISI-Number WOS:000256352700008
Document type (ISI) Journal Article
 
   

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