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Bariatric Surgery Induces Disruption in Inflammatory Signaling Pathways Mediated by Immune Cells in Adipose Tissue: A RNA-Seq Study
BACKGROUND: Bariatric surgery is associated to improvements in obesity-associated comorbidities thought to be mediated by a decrease of adipose inflammation. However, the molecular mechanisms behind these beneficial effects are poorly understood. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed RNA-seq e...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4418598/ https://www.ncbi.nlm.nih.gov/pubmed/25938420 http://dx.doi.org/10.1371/journal.pone.0125718 |
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author | Poitou, Christine Perret, Claire Mathieu, François Truong, Vinh Blum, Yuna Durand, Hervé Alili, Rohia Chelghoum, Nadjim Pelloux, Véronique Aron-Wisnewsky, Judith Torcivia, Adriana Bouillot, Jean-Luc Parks, Brian W. Ninio, Ewa Clément, Karine Tiret, Laurence |
author_facet | Poitou, Christine Perret, Claire Mathieu, François Truong, Vinh Blum, Yuna Durand, Hervé Alili, Rohia Chelghoum, Nadjim Pelloux, Véronique Aron-Wisnewsky, Judith Torcivia, Adriana Bouillot, Jean-Luc Parks, Brian W. Ninio, Ewa Clément, Karine Tiret, Laurence |
author_sort | Poitou, Christine |
collection | PubMed |
description | BACKGROUND: Bariatric surgery is associated to improvements in obesity-associated comorbidities thought to be mediated by a decrease of adipose inflammation. However, the molecular mechanisms behind these beneficial effects are poorly understood. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed RNA-seq expression profiles in adipose tissue from 22 obese women before and 3 months after surgery. Of 15,972 detected genes, 1214 were differentially expressed after surgery at a 5% false discovery rate. Upregulated genes were mostly involved in the basal cellular machinery. Downregulated genes were enriched in metabolic functions of adipose tissue. At baseline, 26 modules of coexpressed genes were identified. The four most stable modules reflected the innate and adaptive immune responses of adipose tissue. A first module reflecting a non-specific signature of innate immune cells, mainly macrophages, was highly conserved after surgery with the exception of DUSP2 and CD300C. A second module reflected the adaptive immune response elicited by T lymphocytes; after surgery, a disconnection was observed between genes involved in T-cell signaling and mediators of the signal transduction such as CXCR1, CXCR2, GPR97, CCR7 and IL7R. A third module reflected neutrophil-mediated inflammation; after surgery, several genes were dissociated from the module, including S100A8, S100A12, CD300E, VNN2, TUBB1 and FAM65B. We also identified a dense network of 19 genes involved in the interferon-signaling pathway which was strongly preserved after surgery, with the exception of DDX60, an antiviral factor involved in RIG-I-mediated interferon signaling. A similar loss of connection was observed in lean mice compared to their obese counterparts. CONCLUSIONS/SIGNIFICANCE: These results suggest that improvements of the inflammatory state following surgery might be explained by a disruption of immuno-inflammatory cascades involving a few crucial molecules which could serve as potential therapeutic targets. |
format | Online Article Text |
id | pubmed-4418598 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-44185982015-05-12 Bariatric Surgery Induces Disruption in Inflammatory Signaling Pathways Mediated by Immune Cells in Adipose Tissue: A RNA-Seq Study Poitou, Christine Perret, Claire Mathieu, François Truong, Vinh Blum, Yuna Durand, Hervé Alili, Rohia Chelghoum, Nadjim Pelloux, Véronique Aron-Wisnewsky, Judith Torcivia, Adriana Bouillot, Jean-Luc Parks, Brian W. Ninio, Ewa Clément, Karine Tiret, Laurence PLoS One Research Article BACKGROUND: Bariatric surgery is associated to improvements in obesity-associated comorbidities thought to be mediated by a decrease of adipose inflammation. However, the molecular mechanisms behind these beneficial effects are poorly understood. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed RNA-seq expression profiles in adipose tissue from 22 obese women before and 3 months after surgery. Of 15,972 detected genes, 1214 were differentially expressed after surgery at a 5% false discovery rate. Upregulated genes were mostly involved in the basal cellular machinery. Downregulated genes were enriched in metabolic functions of adipose tissue. At baseline, 26 modules of coexpressed genes were identified. The four most stable modules reflected the innate and adaptive immune responses of adipose tissue. A first module reflecting a non-specific signature of innate immune cells, mainly macrophages, was highly conserved after surgery with the exception of DUSP2 and CD300C. A second module reflected the adaptive immune response elicited by T lymphocytes; after surgery, a disconnection was observed between genes involved in T-cell signaling and mediators of the signal transduction such as CXCR1, CXCR2, GPR97, CCR7 and IL7R. A third module reflected neutrophil-mediated inflammation; after surgery, several genes were dissociated from the module, including S100A8, S100A12, CD300E, VNN2, TUBB1 and FAM65B. We also identified a dense network of 19 genes involved in the interferon-signaling pathway which was strongly preserved after surgery, with the exception of DDX60, an antiviral factor involved in RIG-I-mediated interferon signaling. A similar loss of connection was observed in lean mice compared to their obese counterparts. CONCLUSIONS/SIGNIFICANCE: These results suggest that improvements of the inflammatory state following surgery might be explained by a disruption of immuno-inflammatory cascades involving a few crucial molecules which could serve as potential therapeutic targets. Public Library of Science 2015-05-04 /pmc/articles/PMC4418598/ /pubmed/25938420 http://dx.doi.org/10.1371/journal.pone.0125718 Text en © 2015 Poitou et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Poitou, Christine Perret, Claire Mathieu, François Truong, Vinh Blum, Yuna Durand, Hervé Alili, Rohia Chelghoum, Nadjim Pelloux, Véronique Aron-Wisnewsky, Judith Torcivia, Adriana Bouillot, Jean-Luc Parks, Brian W. Ninio, Ewa Clément, Karine Tiret, Laurence Bariatric Surgery Induces Disruption in Inflammatory Signaling Pathways Mediated by Immune Cells in Adipose Tissue: A RNA-Seq Study |
title | Bariatric Surgery Induces Disruption in Inflammatory Signaling Pathways Mediated by Immune Cells in Adipose Tissue: A RNA-Seq Study |
title_full | Bariatric Surgery Induces Disruption in Inflammatory Signaling Pathways Mediated by Immune Cells in Adipose Tissue: A RNA-Seq Study |
title_fullStr | Bariatric Surgery Induces Disruption in Inflammatory Signaling Pathways Mediated by Immune Cells in Adipose Tissue: A RNA-Seq Study |
title_full_unstemmed | Bariatric Surgery Induces Disruption in Inflammatory Signaling Pathways Mediated by Immune Cells in Adipose Tissue: A RNA-Seq Study |
title_short | Bariatric Surgery Induces Disruption in Inflammatory Signaling Pathways Mediated by Immune Cells in Adipose Tissue: A RNA-Seq Study |
title_sort | bariatric surgery induces disruption in inflammatory signaling pathways mediated by immune cells in adipose tissue: a rna-seq study |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4418598/ https://www.ncbi.nlm.nih.gov/pubmed/25938420 http://dx.doi.org/10.1371/journal.pone.0125718 |
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