title: Depot Dependent Effects of Dexamethasone on Gene Expression in Human Omental and Abdominal Subcutaneous Adipose Tissues from Obese Women.
abstract: Glucocorticoids promote fat accumulation in visceral compared to subcutaneous depots, but the molecular mechanisms involved remain poorly understood. To identify long-term changes in gene expression that are differentially sensitive or responsive to glucocorticoids in these depots, paired samples of human omental (Om) and abdominal subcutaneous (Abdsc) adipose tissues obtained from obese women during elective surgery were cultured with the glucocorticoid receptor agonist dexamethasone (Dex, 0, 1, 10, 25 and 1000 nM) for 7 days. Dex regulated 32% of the 19,741 genes on the array, while 53% differed by Depot and 2.5% exhibited a Depot*Dex concentration interaction. Gene set enrichment analysis showed Dex regulation of the expected metabolic and inflammatory pathways in both depots. Cluster analysis of the 460 transcripts that exhibited an interaction of Depot and Dex concentration revealed sets of mRNAs for which the responses to Dex differed in magnitude, sensitivity or direction between the two depots as well as mRNAs that responded to Dex only in one depot. These transcripts were also clearly depot different in fresh adipose tissue and are implicated in processes that could affect adipose tissue distribution or functions (e.g. adipogenesis, triacylglycerol synthesis and storage, insulin action). Elucidation of the mechanisms underlying the depot differences in the effect of Dex on the expression of specific genes and pathways that regulate adipose function may offer novel insights into understanding the biology of visceral adipose tissues and their links to metabolic health.
authors.affiliation: Obesity Center, Department of Medicine, Boston University School of Medicine, Boston, MA, United States of America.
authors.forename: R Taylor
authors.identifier: http://orcid.org/0000-0002-5243-4068
authors.initials: RT
authors.lastname: Pickering
authors.affiliation: Obesity Center, Department of Medicine, Boston University School of Medicine, Boston, MA, United States of America.
authors.forename: Mi-Jeong
authors.initials: MJ
authors.lastname: Lee
authors.affiliation: Obesity Center, Department of Medicine, Boston University School of Medicine, Boston, MA, United States of America.
authors.forename: Kalypso
authors.initials: K
authors.lastname: Karastergiou
authors.affiliation: Clinical Translational Sciences Institute, Boston University, Boston, MA, United States of America.
authors.forename: Adam
authors.initials: A
authors.lastname: Gower
authors.affiliation: Obesity Center, Department of Medicine, Boston University School of Medicine, Boston, MA, United States of America.
authors.forename: Susan K
authors.initials: SK
authors.lastname: Fried
mesh_terms: D050156:Adipogenesis / Q000187:drug effects; D000273:Adipose Tissue / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D002478:Cells, Cultured; D003692:Delayed-Action Preparations / Q000737:chemistry; D003907:Dexamethasone / Q000494:pharmacology*; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D009765:Obesity / Q000378:metabolism / Q000473:pathology*; D020411:Oligonucleotide Array Sequence Analysis; D009852:Omentum / Q000166:cytology; D010729:Phosphoenolpyruvate Carboxykinase (GTP) / Q000235:genetics / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000819:agonists / Q000378:metabolism; D050507:Subcutaneous Fat, Abdominal / Q000166:cytology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
chemical_list: D000893:Anti-Inflammatory Agents; D003692:Delayed-Action Preparations; D015850:Interleukin-6; D047908:Intracellular Signaling Peptides and Proteins; D011965:Receptors, Glucocorticoid; C404226:TSC22D3 protein, human; D014157:Transcription Factors; D003907:Dexamethasone; C521898:PCK1 protein, human; D010729:Phosphoenolpyruvate Carboxykinase (GTP)