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We hypothesized that the major metabolic effects of corticosteroids are mediated by changes in the key metabolic enzyme adenosine monophosphate\u2010activated 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\u2010excess model as well as in\n                    <jats:italic>in vitro<\/jats:italic>\n                    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\n                    <jats:italic>in vitro<\/jats:italic>\n                    in the primary adipose and hypothalamic cells and in the liver cell line. Metformin, a known AMPK regulator, prevented the corticosteroidinduced effects on AMPK in human adipocytes and rat hypothalamic neurons. Our data suggest that glucocorticoid\u2010induced 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.\u2014 Christ\u2010Crain M., Kola, B., Lolli F., Fekete, C., Seboek, D., Wittmann, G., Feltrin, D., Igreja, S. C., Ajodha, S., Harvey\u2010White, J., Kunos, G., M\u00fcller B., Pralong, F., Aubert, G., Arnaldi, G., Giacchetti, G., Boscaro, M., Grossman, A. B., Korbonits M. AMP\u2010activated protein kinase mediates glucocorticoidinduced metabolic changes: a novel mechanism in Cushing's syndrome.\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    22, 1672\u20131683 (2008)\n                  <\/jats:p>","DOI":"10.1096\/fj.07-094144","type":"journal-article","created":{"date-parts":[[2008,1,15]],"date-time":"2008-01-15T22:34:36Z","timestamp":1200436476000},"page":"1672-1683","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":139,"title":["AMP\u2010activated protein kinase mediates glucocorticoid\u2010 induced metabolic changes: a novel mechanism in Cushing's syndrome"],"prefix":"10.1096","volume":"22","author":[{"given":"Mirjam","family":"Christ\u2010Crain","sequence":"first","affiliation":[{"name":"Department of Endocrinology William Harvey Research Institute Barts and the London Queen Mary's School of Medicine University of London London UK"}]},{"given":"Blerina","family":"Kola","sequence":"additional","affiliation":[{"name":"Department of Endocrinology William Harvey Research Institute Barts and the London Queen Mary's School of Medicine University of London London UK"}]},{"given":"Francesca","family":"Lolli","sequence":"additional","affiliation":[{"name":"Department of Endocrinology William Harvey Research Institute Barts and the London Queen Mary's School of Medicine University of London London UK"}]},{"given":"Csaba","family":"Fekete","sequence":"additional","affiliation":[{"name":"Department of Endocrine Neurobiology Institute of Experimental Medicine Hungarian Academy of Sciences Budapest Hungary"}]},{"given":"Dalma","family":"Seboek","sequence":"additional","affiliation":[{"name":"Division of Endocrinology Diabetes and Clinical Nutrition University Hospital Basel Switzerland"}]},{"given":"G\u00e1bor","family":"Wittmann","sequence":"additional","affiliation":[{"name":"Department of Endocrine Neurobiology Institute of Experimental Medicine Hungarian Academy of Sciences Budapest Hungary"},{"name":"Tupper Research Institute and Department of Medicine Division of Endocrinology, Diabetes, Metabolism and Molecular Medicine Tufts\u2010New England Medical Center Boston Massachusetts USA"}]},{"given":"Daniel","family":"Feltrin","sequence":"additional","affiliation":[{"name":"Department of Endocrinology William Harvey Research Institute Barts and the London Queen Mary's School of Medicine University of London London UK"}]},{"given":"Susana C.","family":"Igreja","sequence":"additional","affiliation":[{"name":"Department of Endocrinology William Harvey Research Institute Barts and the London Queen Mary's School of Medicine University of London London UK"}]},{"given":"Sharon","family":"Ajodha","sequence":"additional","affiliation":[{"name":"Department of Endocrinology William Harvey Research Institute Barts and the London Queen Mary's School of Medicine University of London London UK"}]},{"given":"Judith","family":"Harvey\u2010White","sequence":"additional","affiliation":[{"name":"Lboratory of Physiologic Studies National Institute on Alcohol Abuse and Alcoholism U.S. National Institutes of Health Bethesda Maryland USA"}]},{"given":"George","family":"Kunos","sequence":"additional","affiliation":[{"name":"Lboratory of Physiologic Studies National Institute on Alcohol Abuse and Alcoholism U.S. National Institutes of Health Bethesda Maryland USA"}]},{"given":"Beat","family":"Muller","sequence":"additional","affiliation":[{"name":"Department of Endocrinology William Harvey Research Institute Barts and the London Queen Mary's School of Medicine University of London London UK"}]},{"given":"Francois","family":"Pralong","sequence":"additional","affiliation":[{"name":"Division of Endocrinology Diabetes and Clinical Nutrition University Hospital Basel Switzerland"}]},{"given":"Gregory","family":"Aubert","sequence":"additional","affiliation":[{"name":"Service d'Endocrinologie Diabetologie et Metabolism Department of Internal Medicine Centre Hospitalier Universitaire Vaudois Lausanne Switzerland"}]},{"given":"Giorgio","family":"Arnaldi","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine University of Ancona Ancona Italy"}]},{"given":"Gilberta","family":"Giacchetti","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine University of Ancona Ancona Italy"}]},{"given":"Marco","family":"Boscaro","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine University of Ancona Ancona Italy"}]},{"given":"Ashley","family":"B. 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