Altered DNA methylation in liver and adipose tissues derived from individuals with obesity and type 2 diabetes.

BACKGROUND: Obesity is a well-recognized risk factor for insulin resistance and type 2 diabetes (T2D), although the precise mechanisms underlying the relationship remain unknown. In this study we identified alterations of DNA methylation influencing T2D pathogenesis, in subcutaneous and visceral adipose tissues, liver, and blood from individuals with obesity. METHODS: The study included individuals with obesity, with and without T2D. From these patients, we obtained samples of liver tissue (n = 16), visceral and subcutaneous adipose tissues (n = 30), and peripheral blood (n = 38). We analyzed DNA methylation using Illumina Infinium Human Methylation arrays, and gene expression profiles using HumanHT-12 Expression BeadChip Arrays. RESULTS: Analysis of DNA methylation profiles revealed several loci with differential methylation between individuals with and without T2D, in all tissues. Aberrant DNA methylation was mainly found in the liver and visceral adipose tissue. Gene ontology analysis of genes with altered DNA methylation revealed enriched terms related to glucose metabolism, lipid metabolism, cell cycle regulation, and response to wounding. An inverse correlation between altered methylation and gene expression in the four tissues was found in a subset of genes, which were related to insulin resistance, adipogenesis, fat storage, and inflammation. CONCLUSIONS: Our present findings provide additional evidence that aberrant DNA methylation may be a relevant mechanism involved in T2D pathogenesis among individuals with obesity

Additional file 1 of Altered DNA methylation in liver and adipose tissues derived from individuals with obesity and type 2 diabetes

Figure S1. Clustering of methylation data from tissue samples from individuals with obesity. Figure S2. Comparison of methylation averages among tissue types. Figure S3. Comparison of DMCs between different tissues. Figure S4. Differential gene expression. Table S1. List of DMCs in WB in the comparison between the DO and NDO groups. Table S2. List of DMCs in SAT in the comparison between the DO and NDO groups. Table S3. List of DMCs in VAT in the comparison between the DO and NDO groups. Table S4. List of DMCs in LT in the comparison between the DO and NDO groups. Table S5. Gene ontology enrichment analysis using the genes with DMCs in SAT. Table S6. Gene ontology enrichment analysis using the genes with DMCs in VAT. Table S7. Gene ontology enrichment analysis using the genes with DMCs in LT. Table S8. Differential gene expression in WB in the comparison between DO and NDO groups. Table S9. Differential gene expression in SAT in the comparison between DO and NDO groups. Table S10. Differential gene expression in VAT in the comparison between DO and NDO groups. Table S11. Differential gene expression in LT in the comparison between DO and NDO groups. Table S12. List of genes with correlation between alteration of DNA methylation and differential gene expression in WB. Table S13. List of genes with correlation between alteration of DNA methylation and differential gene expression in SAT. Table S14. List of genes with correlation between alteration of DNA methylation and differential gene expression in VAT. Table S15. List of genes with correlation between alteration of DNA methylation and differential gene expression in LT. Table S16. Gene ontology enrichment analysis using the genes with correlation between alteration of DNA methylation and differential gene expression. (PDF 3440 kb