Alterations of DNA methylation profile in proximal jejunum potentially contribute to the beneficial effects of gastric bypass in a diabetic rat model
Published on Aug 1, 2019in Surgery for Obesity and Related Diseases3.758
· DOI :10.1016/J.SOARD.2019.05.027
Abstract Background The foregut theory posits that proximal small intestine plays an important role in the improvement of type 2 diabetes (T2D) after Roux-en-Y gastric bypass (RYGB). Objective To study the possible role of proximal jejunum in the treatment of T2D after RYGB via the analysis of DNA methylation and transcriptome. Setting Laboratories of Diabetes Institute. Methods Two batches of T2D rats undergoing surgeries (RYGB, and sham operation as control) were established independently. The proximal jejuna from one batch were used for the methylated DNA immunoprecipitation sequencing (MeDIP-seq) and transcriptome sequencing (RNA-seq). Those from another batch were used for DNA methylation analysis via a MassARRAY platform and quantitative polymerase chain reaction (qPCR) to verify the results of high-throughput sequencing analysis. Results The RNA-seq results showed that the genes differentially expressed (p 2). The Mogat3 in proximal jejunum after RYGB was obviously hypermethylated in the promoter region and its transcription level was significantly reduced. The results of the high-throughput sequencing were validated via methylation quantitative analysis and qPCR in a new set of samples. Conclusions RYGB could change DNA methylation and gene expression profiles in the proximal jejunum in T2D rats. Mogat3 potentially contributes to the beneficial effects caused by RYGB.