Depot Dependent Effects of Dexamethasone on Gene Expression in Human Omental and Abdominal Subcutaneous Adipose Tissues from Obese Women
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...
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| description | 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. |
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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.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0167337</identifier><identifier>PMID: 28005982</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Abdomen ; Adipocytes ; Adipogenesis ; Adipogenesis - drug effects ; Adipose tissue ; Adipose Tissue - cytology ; Adipose Tissue - drug effects ; Adipose Tissue - metabolism ; Adult ; Anti-Inflammatory Agents - pharmacology ; Binding sites ; Bioinformatics ; Biology and Life Sciences ; Cell culture ; Cells, Cultured ; Cluster analysis ; Delayed-Action Preparations - chemistry ; Dexamethasone ; Dexamethasone - pharmacology ; Diabetes ; Directional sensitivity ; Female ; Gene expression ; Gene Expression - drug effects ; Gene set enrichment analysis ; Genes ; Glucocorticoids ; Humans ; Inflammation ; Insulin ; Insulin resistance ; Interleukin-6 - genetics ; Interleukin-6 - metabolism ; Intracellular Signaling Peptides and Proteins - genetics ; Intracellular Signaling Peptides and Proteins - metabolism ; Medicine ; Medicine and Health Sciences ; Metabolism ; Middle Aged ; Molecular modelling ; Obesity ; Obesity - metabolism ; Obesity - pathology ; Oligonucleotide Array Sequence Analysis ; Omentum - cytology ; Phosphoenolpyruvate Carboxykinase (GTP) - genetics ; Phosphoenolpyruvate Carboxykinase (GTP) - metabolism ; Receptors, Glucocorticoid - agonists ; Receptors, Glucocorticoid - metabolism ; Rodents ; Steroids ; Studies ; Subcutaneous Fat, Abdominal - cytology ; Surgery ; Tissues ; Transcription Factors - genetics ; Transcription Factors - metabolism ; Triglycerides ; Young Adult</subject><ispartof>PloS one, 2016-12, Vol.11 (12), p.e0167337</ispartof><rights>2016 Pickering et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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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). 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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.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>28005982</pmid><doi>10.1371/journal.pone.0167337</doi><orcidid>https://orcid.org/0000-0002-5243-4068</orcidid><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS); EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Abdomen Adipocytes Adipogenesis Adipogenesis - drug effects Adipose tissue Adipose Tissue - cytology Adipose Tissue - drug effects Adipose Tissue - metabolism Adult Anti-Inflammatory Agents - pharmacology Binding sites Bioinformatics Biology and Life Sciences Cell culture Cells, Cultured Cluster analysis Delayed-Action Preparations - chemistry Dexamethasone Dexamethasone - pharmacology Diabetes Directional sensitivity Female Gene expression Gene Expression - drug effects Gene set enrichment analysis Genes Glucocorticoids Humans Inflammation Insulin Insulin resistance Interleukin-6 - genetics Interleukin-6 - metabolism Intracellular Signaling Peptides and Proteins - genetics Intracellular Signaling Peptides and Proteins - metabolism Medicine Medicine and Health Sciences Metabolism Middle Aged Molecular modelling Obesity Obesity - metabolism Obesity - pathology Oligonucleotide Array Sequence Analysis Omentum - cytology Phosphoenolpyruvate Carboxykinase (GTP) - genetics Phosphoenolpyruvate Carboxykinase (GTP) - metabolism Receptors, Glucocorticoid - agonists Receptors, Glucocorticoid - metabolism Rodents Steroids Studies Subcutaneous Fat, Abdominal - cytology Surgery Tissues Transcription Factors - genetics Transcription Factors - metabolism Triglycerides Young Adult |
| title | Depot Dependent Effects of Dexamethasone on Gene Expression in Human Omental and Abdominal Subcutaneous Adipose Tissues from Obese Women |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-17T07%3A43%3A58IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Depot%20Dependent%20Effects%20of%20Dexamethasone%20on%20Gene%20Expression%20in%20Human%20Omental%20and%20Abdominal%20Subcutaneous%20Adipose%20Tissues%20from%20Obese%20Women&rft.jtitle=PloS%20one&rft.au=Pickering,%20R%20Taylor&rft.date=2016-12-01&rft.volume=11&rft.issue=12&rft.spage=e0167337&rft.pages=e0167337-&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0167337&rft_dat=%3Cproquest_plos_%3E1859486536%3C/proquest_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1851683541&rft_id=info:pmid/28005982&rft_doaj_id=oai_doaj_org_article_ff78e1b93fa34ed7868ddd8d113e0715&rfr_iscdi=true |