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
Elaheh Mirzaeicheshmeh, Carlos Zerrweck, Federico Centeno-Cruz, Paulina Baca-Peynado, Angélica Martínez‐Hernández, Humberto Garcia‐Ortíz, Cecilia Contreras-Cubas, María Guadalupe Salas-Martínez, Yolanda Saldaña‐Alvarez, Elvia Mendoza‐Caamal, Francisco Barajas‐Olmos, Lorena Orozco
Abstract
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.