Parrillo Luca, Spinelli Rosa, Longo Michele, Desiderio Antonella, Mirra Paola, Nigro Cecilia, Fiory Francesca, Hedjazifar Shahram, Mutarelli Margherita, Carissimo Annamaria, Formisano Pietro, Miele Claudia, Smith Ulf, Raciti Gregory Alexander, Beguinot Francesco
URT Genomics of Diabetes-IEOS, CNR & Department of Translational Medicine - Federico II University of Naples, 80131, Italy.
Lundberg Laboratory for Diabetes Research, Department of Molecular & Clinical Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, 41345, Sweden.
Epigenomics. 2020 May;12(10):873-888. doi: 10.2217/epi-2019-0267. Epub 2020 Jun 2.
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.
2型糖尿病（T2D）患者的一级亲属（FDR）具有脂肪生成受限的特征，这使他们更容易患T2D。表观遗传学可能导致这些异常。分别通过甲基化DNA免疫沉淀测序（MeDIP）和RNA测序对FDR前脂肪细胞和转录组进行了研究。分析揭示了FDR中2841个差异甲基化区域（DMR）。大多数DMR定位于基因体且发生低甲基化。在该基因的一个内含子DMR中鉴定到最强的低甲基化信号。通过亚硫酸氢盐测序证实了FDR中的低甲基化，并且这导致了其表达上调。有趣的是，在3T3-L1前脂肪细胞中过表达抑制了脂肪生成。值得注意的是，在来自相同FDR个体的外周血白细胞中，经验证的与相关的DMR显著低甲基化。最后，肥胖个体中也复制了甲基化模式。我们的研究结果表明在抑制脂肪生成中存在先前未被认识到的作用。这种异常可能导致FDR患T2D的倾向增加。
