Alterations of DNA methylation during adipogenesis differentiation of mesenchymal stem cells isolated from adipose tissue of patients with obesity is associated with type 2 diabetes

Adipogenesis regulation is crucial for mature adipocyte function. In obesity, a major driver of type 2 diabetes (T2D), this process is disrupted and remains poorly characterized. Here we identified altered DNA methylation profiles in diabetic obese patients, during three adipocytes differentiation s...

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Autores principales: Elaheh Mirzaeicheshmeh, Carlos Zerrweck, Federico Centeno-Cruz, Paulina Baca-Peynado, Angélica Martinez-Hernandez, Humberto García-Ortiz, Cecilia Contreras-Cubas, María Guadalupe Salas-Martínez, Yolanda Saldaña-Alvarez, Elvia C. Mendoza-Caamal, Francisco Barajas-Olmos, Lorena Orozco
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Publicado: Taylor & Francis Group 2021
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Acceso en línea:https://doaj.org/article/ed378195d09546b59a8bcf02ff88a8be
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spelling oai:doaj.org-article:ed378195d09546b59a8bcf02ff88a8be2021-11-04T15:00:45ZAlterations of DNA methylation during adipogenesis differentiation of mesenchymal stem cells isolated from adipose tissue of patients with obesity is associated with type 2 diabetes2162-39452162-397X10.1080/21623945.2021.1978157https://doaj.org/article/ed378195d09546b59a8bcf02ff88a8be2021-01-01T00:00:00Zhttp://dx.doi.org/10.1080/21623945.2021.1978157https://doaj.org/toc/2162-3945https://doaj.org/toc/2162-397XAdipogenesis regulation is crucial for mature adipocyte function. In obesity, a major driver of type 2 diabetes (T2D), this process is disrupted and remains poorly characterized. Here we identified altered DNA methylation profiles in diabetic obese patients, during three adipocytes differentiation stages. We isolated mesenchymal cells from visceral adipose tissue of obese patients with and without T2D to analyse DNA methylation profiles at 0, 3, and 18 days of ex vivo differentiation and documented their impact on gene expression. Methylation and gene expression were analysed with EPIC and Clarion S arrays, respectively. Patients with T2D had epigenetic alterations in all the analysed stages, and these were mainly observed in genes important in adipogenesis, insulin resistance, cell death programming, and immune effector processes. Importantly, at 3 days, we found six-fold more methylated CpG alterations than in the other stages. This is the first study to document epigenetic markers that persist through all three adipogenesis stages and their impact on gene expression, which could be a cellular metabolic memory involved in T2D. Our data provided evidence that, throughout the adipogenesis process, alterations occur in methylation that might impact mature adipocyte function, cause tissue malfunction, and potentially, lead to the development of T2D.Elaheh MirzaeicheshmehCarlos ZerrweckFederico Centeno-CruzPaulina Baca-PeynadoAngélica Martinez-HernandezHumberto García-OrtizCecilia Contreras-CubasMaría Guadalupe Salas-MartínezYolanda Saldaña-AlvarezElvia C. Mendoza-CaamalFrancisco Barajas-OlmosLorena OrozcoTaylor & Francis Grouparticleadipogenesistype 2 diabetesobesitydna methylationDiseases of the endocrine glands. Clinical endocrinologyRC648-665CytologyQH573-671PhysiologyQP1-981ENAdipocyte, Vol 10, Iss 1, Pp 493-504 (2021)
institution DOAJ
collection DOAJ
language EN
topic adipogenesis
type 2 diabetes
obesity
dna methylation
Diseases of the endocrine glands. Clinical endocrinology
RC648-665
Cytology
QH573-671
Physiology
QP1-981
spellingShingle adipogenesis
type 2 diabetes
obesity
dna methylation
Diseases of the endocrine glands. Clinical endocrinology
RC648-665
Cytology
QH573-671
Physiology
QP1-981
Elaheh Mirzaeicheshmeh
Carlos Zerrweck
Federico Centeno-Cruz
Paulina Baca-Peynado
Angélica Martinez-Hernandez
Humberto García-Ortiz
Cecilia Contreras-Cubas
María Guadalupe Salas-Martínez
Yolanda Saldaña-Alvarez
Elvia C. Mendoza-Caamal
Francisco Barajas-Olmos
Lorena Orozco
Alterations of DNA methylation during adipogenesis differentiation of mesenchymal stem cells isolated from adipose tissue of patients with obesity is associated with type 2 diabetes
description Adipogenesis regulation is crucial for mature adipocyte function. In obesity, a major driver of type 2 diabetes (T2D), this process is disrupted and remains poorly characterized. Here we identified altered DNA methylation profiles in diabetic obese patients, during three adipocytes differentiation stages. We isolated mesenchymal cells from visceral adipose tissue of obese patients with and without T2D to analyse DNA methylation profiles at 0, 3, and 18 days of ex vivo differentiation and documented their impact on gene expression. Methylation and gene expression were analysed with EPIC and Clarion S arrays, respectively. Patients with T2D had epigenetic alterations in all the analysed stages, and these were mainly observed in genes important in adipogenesis, insulin resistance, cell death programming, and immune effector processes. Importantly, at 3 days, we found six-fold more methylated CpG alterations than in the other stages. This is the first study to document epigenetic markers that persist through all three adipogenesis stages and their impact on gene expression, which could be a cellular metabolic memory involved in T2D. Our data provided evidence that, throughout the adipogenesis process, alterations occur in methylation that might impact mature adipocyte function, cause tissue malfunction, and potentially, lead to the development of T2D.
format article
author Elaheh Mirzaeicheshmeh
Carlos Zerrweck
Federico Centeno-Cruz
Paulina Baca-Peynado
Angélica Martinez-Hernandez
Humberto García-Ortiz
Cecilia Contreras-Cubas
María Guadalupe Salas-Martínez
Yolanda Saldaña-Alvarez
Elvia C. Mendoza-Caamal
Francisco Barajas-Olmos
Lorena Orozco
author_facet Elaheh Mirzaeicheshmeh
Carlos Zerrweck
Federico Centeno-Cruz
Paulina Baca-Peynado
Angélica Martinez-Hernandez
Humberto García-Ortiz
Cecilia Contreras-Cubas
María Guadalupe Salas-Martínez
Yolanda Saldaña-Alvarez
Elvia C. Mendoza-Caamal
Francisco Barajas-Olmos
Lorena Orozco
author_sort Elaheh Mirzaeicheshmeh
title Alterations of DNA methylation during adipogenesis differentiation of mesenchymal stem cells isolated from adipose tissue of patients with obesity is associated with type 2 diabetes
title_short Alterations of DNA methylation during adipogenesis differentiation of mesenchymal stem cells isolated from adipose tissue of patients with obesity is associated with type 2 diabetes
title_full Alterations of DNA methylation during adipogenesis differentiation of mesenchymal stem cells isolated from adipose tissue of patients with obesity is associated with type 2 diabetes
title_fullStr Alterations of DNA methylation during adipogenesis differentiation of mesenchymal stem cells isolated from adipose tissue of patients with obesity is associated with type 2 diabetes
title_full_unstemmed Alterations of DNA methylation during adipogenesis differentiation of mesenchymal stem cells isolated from adipose tissue of patients with obesity is associated with type 2 diabetes
title_sort alterations of dna methylation during adipogenesis differentiation of mesenchymal stem cells isolated from adipose tissue of patients with obesity is associated with type 2 diabetes
publisher Taylor & Francis Group
publishDate 2021
url https://doaj.org/article/ed378195d09546b59a8bcf02ff88a8be
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