Journal Article

Altered PTPRD DNA Methylation Associates with Restricted Adipogenesis in Healthy First-Degree Relatives of Type 2 Diabetes Subjects

Carissimo, Annamaria, Spinelli, Rosa, Mirra, Paola, Fiory, Francesca, Parrillo, Luca, Longo, Michele, Miele, Claudia, Smith, Ulf, Raciti, Gregory Alexander, Beguinot, Francesco, Mutarelli, Margherita, Formisano, Pietro, Desiderio, Antonella, Hedjazifar, Shahram, Nigro, Cecilia

2020

Overview

First-degree relatives (FDR) of individuals with Type 2 diabetes (T2D) feature restricted adipogenesis, which render them more vulnerable to T2D. Epigenetics may contribute to these abnormalities. FDR pre-adipocyte and Transcriptome were investigated by MeDIP- and RNA-Seq, respectively. analysis revealed 2841 differentially methylated regions (DMR) in FDR. Most DMR localized into gene-body and were hypomethylated. The strongest hypomethylation signal was identified in an intronic-DMR at the gene. hypomethylation in FDR was confirmed by bisulphite sequencing and was responsible for its upregulation. Interestingly, -overexpression in 3T3-L1 pre-adipocytes inhibited adipogenesis. Notably, the validated -associated DMR was significantly hypomethylated in peripheral blood leukocytes from the same FDR individuals. Finally, methylation pattern was also replicated in obese individuals. Our findings indicated a previously unrecognized role of in restraining adipogenesis. This abnormality may contribute to increase FDR proclivity toward T2D.

• Subject: adipose tissue / differentiation / DNA methylation / dnmt3a / Endocrinology and Diabetes / Endokrinologi och diabetes / epigenetics / family-history / gene expression / Genetics & Heredity / insulin sensitivity / obesity / pre-adipocyte / preadipocyte / risk / stem-cells / Type 2 diabetes / tyrosine-phosphatase / white adipose-tissue