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Altered DNA methylation in liver and adipose tissues derived from individuals with obesity and type 2 diabetes

BACKGROUND: Obesity is a well-recognized risk factor for insulin resistance and type 2 diabetes (T2D), although the precise mechanisms underlying the relationship remain unknown. In this study we identified alterations of DNA methylation influencing T2D pathogenesis, in subcutaneous and visceral adi...

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Autores principales: Barajas-Olmos, Francisco, Centeno-Cruz, Federico, Zerrweck, Carlos, Imaz-Rosshandler, Iván, Martínez-Hernández, Angélica, Cordova, Emilio J., Rangel-Escareño, Claudia, Gálvez, Faustino, Castillo, Armando, Maydón, Hernán, Campos, Francisco, Maldonado-Pintado, Diana Gabriela, Orozco, Lorena
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5822594/
https://www.ncbi.nlm.nih.gov/pubmed/29466957
http://dx.doi.org/10.1186/s12881-018-0542-8
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author Barajas-Olmos, Francisco
Centeno-Cruz, Federico
Zerrweck, Carlos
Imaz-Rosshandler, Iván
Martínez-Hernández, Angélica
Cordova, Emilio J.
Rangel-Escareño, Claudia
Gálvez, Faustino
Castillo, Armando
Maydón, Hernán
Campos, Francisco
Maldonado-Pintado, Diana Gabriela
Orozco, Lorena
author_facet Barajas-Olmos, Francisco
Centeno-Cruz, Federico
Zerrweck, Carlos
Imaz-Rosshandler, Iván
Martínez-Hernández, Angélica
Cordova, Emilio J.
Rangel-Escareño, Claudia
Gálvez, Faustino
Castillo, Armando
Maydón, Hernán
Campos, Francisco
Maldonado-Pintado, Diana Gabriela
Orozco, Lorena
author_sort Barajas-Olmos, Francisco
collection PubMed
description BACKGROUND: Obesity is a well-recognized risk factor for insulin resistance and type 2 diabetes (T2D), although the precise mechanisms underlying the relationship remain unknown. In this study we identified alterations of DNA methylation influencing T2D pathogenesis, in subcutaneous and visceral adipose tissues, liver, and blood from individuals with obesity. METHODS: The study included individuals with obesity, with and without T2D. From these patients, we obtained samples of liver tissue (n = 16), visceral and subcutaneous adipose tissues (n = 30), and peripheral blood (n = 38). We analyzed DNA methylation using Illumina Infinium Human Methylation arrays, and gene expression profiles using HumanHT-12 Expression BeadChip Arrays. RESULTS: Analysis of DNA methylation profiles revealed several loci with differential methylation between individuals with and without T2D, in all tissues. Aberrant DNA methylation was mainly found in the liver and visceral adipose tissue. Gene ontology analysis of genes with altered DNA methylation revealed enriched terms related to glucose metabolism, lipid metabolism, cell cycle regulation, and response to wounding. An inverse correlation between altered methylation and gene expression in the four tissues was found in a subset of genes, which were related to insulin resistance, adipogenesis, fat storage, and inflammation. CONCLUSIONS: Our present findings provide additional evidence that aberrant DNA methylation may be a relevant mechanism involved in T2D pathogenesis among individuals with obesity. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12881-018-0542-8) contains supplementary material, which is available to authorized users.
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spelling pubmed-58225942018-02-26 Altered DNA methylation in liver and adipose tissues derived from individuals with obesity and type 2 diabetes Barajas-Olmos, Francisco Centeno-Cruz, Federico Zerrweck, Carlos Imaz-Rosshandler, Iván Martínez-Hernández, Angélica Cordova, Emilio J. Rangel-Escareño, Claudia Gálvez, Faustino Castillo, Armando Maydón, Hernán Campos, Francisco Maldonado-Pintado, Diana Gabriela Orozco, Lorena BMC Med Genet Research Article BACKGROUND: Obesity is a well-recognized risk factor for insulin resistance and type 2 diabetes (T2D), although the precise mechanisms underlying the relationship remain unknown. In this study we identified alterations of DNA methylation influencing T2D pathogenesis, in subcutaneous and visceral adipose tissues, liver, and blood from individuals with obesity. METHODS: The study included individuals with obesity, with and without T2D. From these patients, we obtained samples of liver tissue (n = 16), visceral and subcutaneous adipose tissues (n = 30), and peripheral blood (n = 38). We analyzed DNA methylation using Illumina Infinium Human Methylation arrays, and gene expression profiles using HumanHT-12 Expression BeadChip Arrays. RESULTS: Analysis of DNA methylation profiles revealed several loci with differential methylation between individuals with and without T2D, in all tissues. Aberrant DNA methylation was mainly found in the liver and visceral adipose tissue. Gene ontology analysis of genes with altered DNA methylation revealed enriched terms related to glucose metabolism, lipid metabolism, cell cycle regulation, and response to wounding. An inverse correlation between altered methylation and gene expression in the four tissues was found in a subset of genes, which were related to insulin resistance, adipogenesis, fat storage, and inflammation. CONCLUSIONS: Our present findings provide additional evidence that aberrant DNA methylation may be a relevant mechanism involved in T2D pathogenesis among individuals with obesity. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12881-018-0542-8) contains supplementary material, which is available to authorized users. BioMed Central 2018-02-21 /pmc/articles/PMC5822594/ /pubmed/29466957 http://dx.doi.org/10.1186/s12881-018-0542-8 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Barajas-Olmos, Francisco
Centeno-Cruz, Federico
Zerrweck, Carlos
Imaz-Rosshandler, Iván
Martínez-Hernández, Angélica
Cordova, Emilio J.
Rangel-Escareño, Claudia
Gálvez, Faustino
Castillo, Armando
Maydón, Hernán
Campos, Francisco
Maldonado-Pintado, Diana Gabriela
Orozco, Lorena
Altered DNA methylation in liver and adipose tissues derived from individuals with obesity and type 2 diabetes
title Altered DNA methylation in liver and adipose tissues derived from individuals with obesity and type 2 diabetes
title_full Altered DNA methylation in liver and adipose tissues derived from individuals with obesity and type 2 diabetes
title_fullStr Altered DNA methylation in liver and adipose tissues derived from individuals with obesity and type 2 diabetes
title_full_unstemmed Altered DNA methylation in liver and adipose tissues derived from individuals with obesity and type 2 diabetes
title_short Altered DNA methylation in liver and adipose tissues derived from individuals with obesity and type 2 diabetes
title_sort altered dna methylation in liver and adipose tissues derived from individuals with obesity and type 2 diabetes
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5822594/
https://www.ncbi.nlm.nih.gov/pubmed/29466957
http://dx.doi.org/10.1186/s12881-018-0542-8
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