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...
Guardado en:
Autores principales: | , , , , , , , , , , , |
---|---|
Formato: | article |
Lenguaje: | EN |
Publicado: |
Taylor & Francis Group
2021
|
Materias: | |
Acceso en línea: | https://doaj.org/article/ed378195d09546b59a8bcf02ff88a8be |
Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
id |
oai:doaj.org-article:ed378195d09546b59a8bcf02ff88a8be |
---|---|
record_format |
dspace |
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 |
work_keys_str_mv |
AT elahehmirzaeicheshmeh alterationsofdnamethylationduringadipogenesisdifferentiationofmesenchymalstemcellsisolatedfromadiposetissueofpatientswithobesityisassociatedwithtype2diabetes AT carloszerrweck alterationsofdnamethylationduringadipogenesisdifferentiationofmesenchymalstemcellsisolatedfromadiposetissueofpatientswithobesityisassociatedwithtype2diabetes AT federicocentenocruz alterationsofdnamethylationduringadipogenesisdifferentiationofmesenchymalstemcellsisolatedfromadiposetissueofpatientswithobesityisassociatedwithtype2diabetes AT paulinabacapeynado alterationsofdnamethylationduringadipogenesisdifferentiationofmesenchymalstemcellsisolatedfromadiposetissueofpatientswithobesityisassociatedwithtype2diabetes AT angelicamartinezhernandez alterationsofdnamethylationduringadipogenesisdifferentiationofmesenchymalstemcellsisolatedfromadiposetissueofpatientswithobesityisassociatedwithtype2diabetes AT humbertogarciaortiz alterationsofdnamethylationduringadipogenesisdifferentiationofmesenchymalstemcellsisolatedfromadiposetissueofpatientswithobesityisassociatedwithtype2diabetes AT ceciliacontrerascubas alterationsofdnamethylationduringadipogenesisdifferentiationofmesenchymalstemcellsisolatedfromadiposetissueofpatientswithobesityisassociatedwithtype2diabetes AT mariaguadalupesalasmartinez alterationsofdnamethylationduringadipogenesisdifferentiationofmesenchymalstemcellsisolatedfromadiposetissueofpatientswithobesityisassociatedwithtype2diabetes AT yolandasaldanaalvarez alterationsofdnamethylationduringadipogenesisdifferentiationofmesenchymalstemcellsisolatedfromadiposetissueofpatientswithobesityisassociatedwithtype2diabetes AT elviacmendozacaamal alterationsofdnamethylationduringadipogenesisdifferentiationofmesenchymalstemcellsisolatedfromadiposetissueofpatientswithobesityisassociatedwithtype2diabetes AT franciscobarajasolmos alterationsofdnamethylationduringadipogenesisdifferentiationofmesenchymalstemcellsisolatedfromadiposetissueofpatientswithobesityisassociatedwithtype2diabetes AT lorenaorozco alterationsofdnamethylationduringadipogenesisdifferentiationofmesenchymalstemcellsisolatedfromadiposetissueofpatientswithobesityisassociatedwithtype2diabetes |
_version_ |
1718444807863402496 |