Alterations of DNA methylation profile in proximal jejunum potentially contribute to the beneficial effects of gastric bypass in a diabetic rat model.

BACKGROUND

The foregut theory posits that the 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

Laboratory of Shanghai Diabetes Institute, China.

METHODS

Two batches of T2D rats undergoing surgeries (RYGB and a sham operation as control) were established independently. The proximal jejuna from one batch were used for the methylated DNA immunoprecipitation sequencing and transcriptome sequencing. Those from another batch were used for DNA methylation analysis via a MassARRAY (Agena Bioscience, San Diego, CA, United States) platform and quantitative polymerase chain reaction to verify the results of high-throughput sequencing analysis.

RESULTS

The transcriptome sequencing results showed that the genes differentially expressed (P < .05) in the RYGB- and sham-operated groups were significantly enriched in the gene ontology biological processes associated with fatty acid metabolism and lipid transport. The methylated DNA immunoprecipitation sequencing analysis showed that there were 1973 genes with significantly differentially methylated CpG sites located within gene promoters between the 2 groups (P < .05 and fold change > 2). The Mogat3 in the proximal jejunum after RYGB was 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 quantitative polymerase chain reaction 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.