Table_1_m6A Regulators in Human Adipose Tissue - Depot-Specificity and Correlation With Obesity.docx

BackgroundN6-methyladenosine (m6A) is one of the most abundant post-transcriptional modifications on mRNA influencing mRNA metabolism. There is emerging evidence for its implication in metabolic disease. No comprehensive analyses on gene expression of m6A regulators in human adipose tissue, especially in paired adipose tissue depots, and its correlation with clinical variables were reported so far. We hypothesized that inter-depot specific gene expression of m6A regulators may differentially correlate with clinical variables related to obesity and fat distribution.MethodsWe extracted intra-individually paired gene expression data (omental visceral adipose tissue (OVAT) N=48; subcutaneous adipose tissue (SAT) N=56) of m6A regulators from an existing microarray dataset. We also measured gene expression in another sample set of paired OVAT and SAT (N=46) using RT-qPCR. Finally, we extracted existing gene expression data from peripheral mononuclear blood cells (PBMCs) and single nucleotide polymorphisms (SNPs) in METTL3 and YTHDF3 from genome wide data from the Sorbs population (N=1049). The data were analysed for differential gene expression between OVAT and SAT; and for association with obesity and clinical variables. We further tested for association of SNP markers with gene expression and clinical traits.ResultsIn adipose tissue we observed that several m6A regulators (WTAP, VIRMA, YTHDC1 and ALKBH5) correlate with obesity and clinical variables. Moreover, we found adipose tissue depot specific gene expression for METTL3, WTAP, VIRMA, FTO and YTHDC1. In PBMCs, we identified ALKBH5 and YTHDF3 correlated with obesity. Genetic markers in METTL3 associate with BMI whilst SNPs in YTHDF3 are associated with its gene expression.ConclusionsOur data show that expression of m6A regulators correlates with obesity, is adipose tissue depot-specific and related to clinical traits. Genetic variation in m6A regulators adds an additional layer of variability to the functional consequences.

背景：N6-甲基腺苷（m6A）是mRNA上最丰富的转录后修饰之一，它影响着mRNA的代谢。目前已有证据表明，m6A在代谢性疾病中扮演着重要角色。迄今为止，尚未有关于人类脂肪组织中m6A调控基因表达的综合分析，尤其是在配对脂肪组织库中，以及其与临床变量的相关性研究。我们假设，脂肪库间特定的m6A调控基因表达可能与肥胖和脂肪分布相关的临床变量存在差异性的相关性。方法：我们从现有的微阵列数据集中提取了个体内配对的m6A调控基因表达数据（内脏脂肪组织（OVAT）N=48；皮下脂肪组织（SAT）N=56）。我们还使用RT-qPCR测量了另一组配对的OVAT和SAT样本（N=46）的基因表达。最后，我们从索布人群体全基因组数据中提取了外周血单个核细胞（PBMCs）的基因表达数据以及METTL3和YTHDF3基因的单核苷酸多态性（SNPs）（N=1049）。对这些数据进行了分析，以比较OVAT和SAT之间的差异基因表达，以及与肥胖和临床变量的关联。我们进一步检测了SNP标记与基因表达和临床特征的关联。结果：在脂肪组织中，我们发现几种m6A调控因子（WTAP、VIRMA、YTHDC1和ALKBH5）与肥胖和临床变量相关。此外，我们还发现了METTL3、WTAP、VIRMA、FTO和YTHDC1在脂肪库中具有特定的基因表达。在PBMCs中，我们确定了ALKBH5和YTHDF3与肥胖相关。METTL3基因中的遗传标记与BMI相关，而YTHDF3基因中的SNPs与其基因表达相关。结论：我们的数据显示，m6A调控因子的表达与肥胖相关，具有脂肪组织库特异性，并与其临床特征相关。m6A调控基因中的遗传变异为m6A调控的功能后果提供了额外的变异层。