Abstract | Background: Deficient glucocorticoid biosynthesis leading to adrenal insufficiency is life-threatening and is associated with significant co-morbidities. The affected pathways underlying the pathophysiology of co-morbidities due to glucocorticoid deficiency remain poorly understood and require further investigation. Methods: To explore the pathophysiological processes related to glucocorticoid deficiency, we have performed global transcriptional, post-transcriptional and metabolic profiling of a cortisol-deficient zebrafish mutant with a disrupted ferredoxin (fdx1b) system. Findings: Interpretation: Our study provides a detailed map of metabolic changes induced by glucocorticoid deficiency as a consequence of a disrupted ferredoxin system in an animal model of adrenal insufficiency. This improved pathophysiological understanding of global glucocorticoid deficiency informs on more targeted translational studies in humans suffering from conditions associated with glucocorticoid deficiency. Fund: Marie Curie Intra-European Fellowships for Career Development, HGF-programme BIFTM, Deutsche Forschungsgemeinschaft, BBSRC.
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Authors | Meltem Weger, Benjamin D Weger, Benjamin Görling, Gernot Poschet, Melek Yildiz, Rüdiger Hell, Burkhard Luy, Teoman Akcay, Tülay Güran, Thomas Dickmeis, Ferenc Müller, Nils Krone |
Journal | EBioMedicine
(EBioMedicine)
Vol. 36
Pg. 376-389
(10 2018)
ISSN: 2352-3964 [Electronic] Netherlands |
PMID | 30266295
(Publication Type: Journal Article)
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Chemical References |
- Glucocorticoids
- Glutamine
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Topics |
- Adrenal Insufficiency
(metabolism)
- Animals
- Animals, Genetically Modified
- Glucocorticoids
(biosynthesis)
- Glutamine
(metabolism)
- Humans
- Metabolic Networks and Pathways
- Metabolomics
- Zebrafish
(genetics, metabolism)
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