title: FKBP5 expression in human adipose tissue increases following dexamethasone exposure and is associated with insulin resistance.
abstract: OBJECTIVE
  To study effects of dexamethasone on gene expression in human adipose tissue aiming to identify potential novel mechanisms for glucocorticoid-induced insulin resistance.
  
  
  METHODS
  Subcutaneous and omental adipose tissue, obtained from non-diabetic donors (10 M/15 F; age: 28-60 years; BMI: 20.7-30.6 kg/m²), was incubated with or without dexamethasone (0.003-3 μmol/L) for 24 h. Gene expression was assessed by microarray and real time-PCR and protein expression by immunoblotting.
  
  
  RESULTS
  FKBP5 (FK506-binding protein 5) and CNR1 (cannabinoid receptor 1) were the most responsive genes to dexamethasone in both subcutaneous and omental adipose tissue (~7-fold). Dexamethasone increased FKBP5 gene and protein expression in a dose-dependent manner in both depots. The gene product, FKBP51 protein, was 10-fold higher in the omental than in the subcutaneous depot, whereas the mRNA levels were similar. Higher FKBP5 gene expression in omental adipose tissue was associated with reduced insulin effects on glucose uptake in both depots. Furthermore, FKBP5 gene expression in subcutaneous adipose tissue was positively correlated with serum insulin, HOMA-IR and subcutaneous adipocyte diameter and negatively with plasma HDL-cholesterol. FKBP5 SNPs were found to be associated with type 2 diabetes and diabetes-related phenotypes in large population-based samples.
  
  
  CONCLUSIONS
  Dexamethasone exposure promotes expression of FKBP5 in adipose tissue, a gene that may be implicated in glucocorticoid-induced insulin resistance.
authors.affiliation: Department of Medical Sciences, Uppsala University, Uppsala, Sweden; Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Pereira
authors.affiliation: Department of Molecular and Clinical Medicine and Sahlgrenska University Hospital, Gothenburg, Sweden.
authors.forename: Jenny
authors.initials: J
authors.lastname: Palming
authors.affiliation: Department of Molecular and Clinical Medicine and Sahlgrenska University Hospital, Gothenburg, Sweden.
authors.forename: Maria K
authors.initials: MK
authors.lastname: Svensson
authors.affiliation: Department of Surgery, Sahlgrenska University Hospital, Gothenburg, Sweden.
authors.forename: Magnus
authors.initials: M
authors.lastname: Rizell
authors.affiliation: Department of Surgery, Frölunda Specialist Hospital, Gothenburg, Sweden.
authors.forename: Jan
authors.initials: J
authors.lastname: Dalenbäck
authors.affiliation: AstraZeneca R&D, Mölndal, Sweden.
authors.forename: Mårten
authors.initials: M
authors.lastname: Hammar
authors.affiliation: Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
authors.forename: Tove
authors.initials: T
authors.lastname: Fall
authors.affiliation: Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
authors.forename: Cherno O
authors.initials: CO
authors.lastname: Sidibeh
authors.affiliation: Department of Molecular and Clinical Medicine and Center for Cardiovascular and Metabolic Research, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Per-Arne
authors.initials: PA
authors.lastname: Svensson
authors.affiliation: Department of Medical Sciences, Uppsala University, Uppsala, Sweden; AstraZeneca R&D, Mölndal, Sweden. Electronic address: jan.eriksson@medsci.uu.se.
authors.forename: Jan W
authors.initials: JW
authors.lastname: Eriksson
mesh_terms: D000328:Adult; D001692:Biological Transport / Q000187:drug effects; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D005938:Glucocorticoids / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000097:blood / Q000494:pharmacology; D007333:Insulin Resistance; D050152:Intra-Abdominal Fat / Q000098:blood supply / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009994:Osmolar Concentration; D012333:RNA, Messenger / Q000378:metabolism; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D017154:Stromal Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D050507:Subcutaneous Fat, Abdominal / Q000098:blood supply / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D022021:Tacrolimus Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000099159:Tacrolimus Binding Protein 5
chemical_list: D003907:Dexamethasone; D005938:Glucocorticoids; D005947:Glucose; D007328:Insulin; D012333:RNA, Messenger; D043884:Receptor, Cannabinoid, CB1; D022021:Tacrolimus Binding Proteins; D000099159:Tacrolimus Binding Protein 5; C571130:CNR1 protein, human
keywords: Adipose tissue; FKBP5; Gene expression; Glucocorticoids; Insulin resistance