Iwaya Chihiro, Kitajima Hidetoshi, Yamamoto Ken, Maeda Yasutaka, Sonoda Noriyuki, Shibata Hiroki, Inoguchi Toyoshi
Division of Genomics, Medical Institute of Bioregulation, Kyushu University, Japan.
Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK.
Biochem Biophys Res Commun. 2018 Mar 11;497(3):908-915. doi: 10.1016/j.bbrc.2017.12.104. Epub 2018 Feb 6.
Krüppel-Like Factor 14 (KLF14) gene, which appears to be a master regulator of gene expression in the adipose tissue and have previously been associated with BMI and Type 2 diabetes (T2D) by large genome-wide association studies. In order to find predictive biomarkers for the development of T2D, it is necessary to take epigenomic changes affected by environmental factors into account. This study focuses on ageing and obesity, which are T2D risk factors, and examines epigenetic changes and inflammatory changes. We investigated DNA methylation changes in the Klf14 promoter region in different organs of mice for comparing aging and weight. We found that methylation levels of these sites were increased with aging and weight in the spleen, the adipose tissue, the kidney, the lung, the colon and the whole blood cells. In addition, in the spleen, the adipose tissue and the whole blood, these epigenetic changes were also significantly associated with inflammatory levels. Moreover, not only Klf14, but also expression levels of some downstream genes were decreased with methylation in the spleen, the adipose tissue and the whole blood cells. Taken together, our results suggest that methylation changes of Klf14 in those tissues may be associated with changes in gene expression and inflammation on the adipose tissue of obesity and T2D. In addition, the methylation changes in the whole blood cells may serve as a predictive epigenetic biomarker for the development of T2D.
Krüppel样因子14（KLF14）基因似乎是脂肪组织中基因表达的主要调节因子，此前通过大规模全基因组关联研究已将其与体重指数和2型糖尿病（T2D）联系起来。为了找到T2D发生发展的预测性生物标志物，有必要考虑受环境因素影响的表观基因组变化。本研究聚焦于作为T2D风险因素的衰老和肥胖，并研究表观遗传变化和炎症变化。我们研究了小鼠不同器官中Klf14启动子区域的DNA甲基化变化，以比较衰老和体重情况。我们发现，在脾脏、脂肪组织、肾脏、肺、结肠和全血细胞中，这些位点的甲基化水平随衰老和体重增加而升高。此外，在脾脏、脂肪组织和全血中，这些表观遗传变化也与炎症水平显著相关。而且，在脾脏、脂肪组织和全血细胞中，不仅Klf14，一些下游基因的表达水平也随甲基化而降低。综上所述，我们的结果表明，这些组织中Klf14的甲基化变化可能与肥胖和T2D脂肪组织中的基因表达变化及炎症有关。此外，全血细胞中的甲基化变化可能作为T2D发生发展的预测性表观遗传生物标志物。
