Glucocorticoid receptor ChIP-sequencing of subcutaneous fat reveals modulation of inflammatory pathways

Obesity (Silver Spring). 2015 Nov;23(11):2286-93. doi: 10.1002/oby.21251. Epub 2015 Sep 26.


Objective: To identify glucocorticoid receptor (GR)-associated chromatin sequences and target genes in primary human abdominal subcutaneous fat.

Methods: GR chromatin immunoprecipitation (ChIP)-sequencing (seq) methodology in subcutaneous human adipocytes treated ex vivo with dexamethasone (dex) was optimized to identify genome-wide dex-dependent GR-binding regions (GBRs). Gene expression analyses were performed in parallel ± dex treatment.

Results: Fat was obtained from four female surgical patients without obesity with a median age of 50.5 years. ChIP-seq analysis revealed 219 dex-associated GBRs. Of these, 136 GBRs were located within 100 kb of the transcriptional start site and associated with 123 genes. Combining these data with dex-induced gene expression, 70 of the 123 putative direct target genes were significantly up- or downregulated following 4 hours of dex treatment. Gene expression analysis demonstrated that the top 10 pathways reflected regulation of cellular metabolism and inflammation. DEPTOR, an inhibitor of mTOR, was identified as a potential direct GR target gene.

Conclusions: This is the first report of genome-wide GR ChIP-seq and gene expression analysis in human fat. The results implicate regulation of key GR target genes that are involved in dampening inflammation and promoting cellular metabolism.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes / drug effects
  • Adipocytes / metabolism
  • Adult
  • Aged, 80 and over
  • Cells, Cultured
  • Chromatin Immunoprecipitation
  • Dexamethasone / pharmacology
  • Female
  • Gene Expression Regulation* / drug effects
  • Humans
  • Inflammation / genetics*
  • Inflammation / metabolism
  • Middle Aged
  • Protein Binding / drug effects
  • Receptors, Glucocorticoid / genetics*
  • Receptors, Glucocorticoid / metabolism*
  • Sequence Analysis, DNA / methods
  • Signal Transduction / drug effects
  • Signal Transduction / genetics
  • Subcutaneous Fat / drug effects
  • Subcutaneous Fat / metabolism*


  • Receptors, Glucocorticoid
  • Dexamethasone