Altered DNA methylation associates with restricted adipogenesis in healthy first-degree relatives of Type 2 diabetes subjects.

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.