Ling Charlotte, Rönn Tina
Epigenetics and Diabetes Unit, Department of Clinical Sciences, Lund University Diabetes Centre, Scania University Hospital, Jan Waldenströms gata 35, 205 02, Malmö, Sweden.
Diabetologia. 2016 Nov;59(11):2295-2297. doi: 10.1007/s00125-016-4109-y. Epub 2016 Sep 20.
Epigenetic variation in human adipose tissue has been linked to type 2 diabetes and its related risk factors including age and obesity. Insulin resistance, a key risk factor for type 2 diabetes, may also be associated with altered DNA methylation in visceral and subcutaneous adipose tissue. Furthermore, linking epigenetic variation in target tissues to similar changes in blood cells may identify new blood-based biomarkers. In this issue of Diabetologia, Arner et al studied the transcriptome and methylome in subcutaneous and visceral adipose tissue of 80 obese women who were either insulin-sensitive or -resistant (DOI 10.1007/s00125-016-4074-5 ). While they found differences in gene expression between the two groups, no alterations in DNA methylation were found after correction for multiple testing. Nevertheless, based on nominal p values, their methylation data overlapped with methylation differences identified in adipose tissue of individuals with type 2 diabetes compared with healthy individuals. Differential methylation of these overlapping CpG sites may predispose to diabetes by occurring already in the insulin-resistant state. Furthermore, some methylation changes may contribute to an inflammatory process in adipose tissue since the identified CpG sites were annotated to genes encoding proteins involved in inflammation. Finally, the methylation pattern in circulating leucocytes did not mirror the adipose tissue methylome of these 80 women. Together, identifying novel molecular mechanisms contributing to insulin resistance and type 2 diabetes may help advance the search for new therapeutic alternatives.
人类脂肪组织中的表观遗传变异与2型糖尿病及其相关风险因素（包括年龄和肥胖）有关。胰岛素抵抗是2型糖尿病的关键风险因素，也可能与内脏和皮下脂肪组织中DNA甲基化的改变有关。此外，将靶组织中的表观遗传变异与血细胞中的类似变化联系起来，可能会发现新的血液生物标志物。在本期《糖尿病学》中，阿纳等人研究了80名肥胖女性皮下和内脏脂肪组织中的转录组和甲基化组，这些女性要么胰岛素敏感，要么胰岛素抵抗（DOI 10.1007/s00125-016-4074-5）。虽然他们发现两组之间基因表达存在差异，但在进行多重检验校正后，未发现DNA甲基化有改变。然而，基于名义p值，他们的甲基化数据与2型糖尿病患者与健康个体相比在脂肪组织中发现的甲基化差异重叠。这些重叠的CpG位点的差异甲基化可能在胰岛素抵抗状态下就已发生，从而易患糖尿病。此外，一些甲基化变化可能会导致脂肪组织中的炎症过程，因为所确定的CpG位点被注释到编码参与炎症的蛋白质的基因上。最后，循环白细胞中的甲基化模式并未反映这80名女性的脂肪组织甲基化组。总之，确定导致胰岛素抵抗和2型糖尿病的新分子机制可能有助于推进寻找新的治疗方案。
