title: Prednisolone induces the Wnt signalling pathway in 3T3-L1 adipocytes.
abstract: Synthetic glucocorticoids are potent anti-inflammatory drugs but show dose-dependent metabolic side effects such as the development of insulin resistance and obesity. The precise mechanisms involved in these glucocorticoid-induced side effects, and especially the participation of adipose tissue in this are not completely understood. We used a combination of transcriptomics, antibody arrays and bioinformatics approaches to characterize prednisolone-induced alterations in gene expression and adipokine secretion, which could underlie metabolic dysfunction in 3T3-L1 adipocytes. Several pathways, including cytokine signalling, Akt signalling, and Wnt signalling were found to be regulated at multiple levels, showing that these processes are targeted by prednisolone. These results suggest that mechanisms by which prednisolone induce insulin resistance include dysregulation of wnt signalling and immune response processes. These pathways may provide interesting targets for the development of improved glucocorticoids.
authors.affiliation: CDD, CMBI, NCMLS, Radboud University Medical Centre, Nijmegen, The Netherlands.
authors.forename: Wilco W M
authors.initials: WW
authors.lastname: Fleuren
authors.forename: Margot M L
authors.initials: MM
authors.lastname: Linssen
authors.forename: Erik J M
authors.initials: EJ
authors.lastname: Toonen
authors.forename: Gerard C M
authors.initials: GC
authors.lastname: van der Zon
authors.forename: Bruno
authors.initials: B
authors.lastname: Guigas
authors.forename: Jacob
authors.initials: J
authors.lastname: de Vlieg
authors.forename: Wim H A
authors.initials: WH
authors.lastname: Dokter
authors.forename: D Margriet
authors.initials: DM
authors.lastname: Ouwens
authors.forename: Wynand
authors.initials: W
authors.lastname: Alkema
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism*; D054392:Adipokines / Q000235:genetics; D000818:Animals; D003847:Deoxyglucose / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D005938:Glucocorticoids / Q000009:adverse effects / Q000494:pharmacology; D007109:Immunity / Q000187:drug effects; D007328:Insulin / Q000494:pharmacology; D007333:Insulin Resistance; D051379:Mice; D011239:Prednisolone / Q000009:adverse effects* / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D046888:Tissue Array Analysis; D059467:Transcriptome / Q000187:drug effects; D060449:Wnt Signaling Pathway / Q000187:drug effects* / Q000235:genetics
chemical_list: D054392:Adipokines; D005938:Glucocorticoids; D007328:Insulin; D003847:Deoxyglucose; D011239:Prednisolone