Prednisolone induced metabolite profiles in human and mouse: Cross-species translation and cross-omics integration.

Prednisolone and other glucocorticoids (GCs) are very potent anti-inflammatory drugs. Although they are very effective, prolonged use is hampered by side effects of which especially metabolic side effects are evident. The molecular mechanisms by which GCs induce metabolic side effects are still largely unknown. To allow for a more rational development of an improved GC it is crucial to understand the molecular mechanisms of these GC induced metabolic side effects both in human as in relevant animal models.

In this project, we aim at deciphering new aspects of GC induced side effects in humans and in mice by use of metabolic and transcriptomic profiling. To that end human healthy volunteers and healthy mice were treated with Prednisolone and metabolomics, transcriptomics and, for human only, proteomics data were collected.
In humans numerous metabolites, including amino acids, sugars and intermediates in energy metabolism were dose dependently regulated by prednisolone. Similar large effects were seen on proteome and transcriptome level. A draft manuscript has been prepared on the statistical analysis and biological interpretation of the data.

First pass analysis of the mouse transcriptomics and metabolomics data showed similar prednisolone induced changes. Detailed analysis of these data is currently going on. 

PD 1-4-10
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Status Project Proposal: 
Approved 14-4-09
Start date: 
April, 2010
Projected end date: 
April, 2013
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