PUBLICATION
Glucocorticoid deficiency causes transcriptional and post-transcriptional reprogramming of glutamine metabolism
- Authors
- Weger, M., Weger, B.D., Görling, B., Poschet, G., Yildiz, M., Hell, R., Luy, B., Akcay, T., Güran, T., Dickmeis, T., Müller, F., Krone, N.
- ID
- ZDB-PUB-180930-1
- Date
- 2018
- Source
- EBioMedicine 36: 376-389 (Journal)
- Registered Authors
- Dickmeis, Thomas, Müller, Ferenc, Weger, Benjamin, Weger, Meltem
- Keywords
- Adrenal insufficiency, Ferredoxin, Oxidative stress, Purine metabolism, Zebrafish
- Datasets
- GEO:GSE107547
- MeSH Terms
-
- Adrenal Insufficiency/metabolism*
- Animals
- Animals, Genetically Modified
- Glucocorticoids/biosynthesis
- Glutamine/metabolism*
- Humans
- Metabolic Networks and Pathways*
- Metabolomics
- Zebrafish/genetics
- Zebrafish/metabolism
- PubMed
- 30266295 Full text @ EBioMedicine
Citation
Weger, M., Weger, B.D., Görling, B., Poschet, G., Yildiz, M., Hell, R., Luy, B., Akcay, T., Güran, T., Dickmeis, T., Müller, F., Krone, N. (2018) Glucocorticoid deficiency causes transcriptional and post-transcriptional reprogramming of glutamine metabolism. EBioMedicine. 36:376-389.
Abstract
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.
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.
fdx1b−/− mutants show pervasive reprogramming of metabolism, in particular of glutamine-dependent pathways such as glutathione metabolism, and exhibit changes of oxidative stress markers. The glucocorticoid-dependent post-transcriptional regulation of key enzymes involved in de novo purine synthesis was also affected in this mutant. Moreover, fdx1b−/− mutants exhibit crucial features of primary adrenal insufficiency, and mirror metabolic changes detected in primary adrenal insufficiency patients.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping