التفاصيل البيبلوغرافية
| العنوان: |
AMP-activated protein kinase mediates glucocorticoid-induced metabolic changes: a novel mechanism in Cushing's syndrome |
| المؤلفون: |
Sharon Ajodha, Gregory Aubert, Csaba Fekete, Dalma Seboek, George Kunos, Judith Harvey-White, Blerina Kola, Daniel Feltrin, Beat Müller, Gábor Wittmann, Susana Igreja, Marco Boscaro, Francesca Lolli, Giorgio Arnaldi, François P. Pralong, Márta Korbonits, Gilberta Giacchetti, Ashley B. Grossman, Mirjam Christ-Crain |
| المصدر: |
FASEB J. |
| سنة النشر: |
2008 |
| مصطلحات موضوعية: |
medicine.medical_specialty, media_common.quotation_subject, Hypothalamus, Adipose tissue, 030209 endocrinology & metabolism, AMP-Activated Protein Kinases, Protein Serine-Threonine Kinases, Biochemistry, Dexamethasone, 03 medical and health sciences, 0302 clinical medicine, AMP-activated protein kinase, Multienzyme Complexes, Internal medicine, Genetics, medicine, Animals, Humans, Protein kinase A, Molecular Biology, Cushing Syndrome, Glucocorticoids, Cells, Cultured, 030304 developmental biology, media_common, 0303 health sciences, biology, Liver cell, Myocardium, AMPK, Appetite, Metformin, 3. Good health, Rats, Endocrinology, Metabolism, Adipose Tissue, Liver, Organ Specificity, biology.protein, obesity insulin resistance lipid metabolism, Glucocorticoid, Biotechnology, medicine.drug |
| الوصف: |
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. |
| DOI: |
10.1096/fj.07-094144 |
| URL الوصول: |
https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e398f7c2d5a5c70d6cd587234c1fd973 |
| Rights: |
OPEN |
| رقم الانضمام: |
edsair.doi.dedup.....e398f7c2d5a5c70d6cd587234c1fd973 |
| قاعدة البيانات: |
OpenAIRE |