Document Type

Journal Article

Publication Date

1-22-2015

Journal

Genome Biology

Volume

Volume 16

Inclusive Pages

Article number 8

Abstract

Background

Environmental factors can influence obesity by epigenetic mechanisms. Adipose tissue plays a key role in obesity-related metabolic dysfunction, and gastric bypass provides a model to investigate obesity and weight loss in humans.

Results

Here, we investigate DNA methylation in adipose tissue from obese women before and after gastric bypass and significant weight loss. In total, 485,577 CpG sites were profiled in matched, before and after weight loss, subcutaneous and omental adipose tissue. A paired analysis revealed significant differential methylation in omental and subcutaneous adipose tissue. A greater proportion of CpGs are hypermethylated before weight loss and increased methylation is observed in the 3′ untranslated region and gene bodies relative to promoter regions. Differential methylation is found within genes associated with obesity, epigenetic regulation and development, such asCETP, FOXP2, HDAC4, DNMT3B, KCNQ1 and HOX clusters. We identify robust correlations between changes in methylation and clinical trait, including associations between fasting glucose andHDAC4, SLC37A3 and DENND1C in subcutaneous adipose. Genes investigated with differential promoter methylation all show significantly different levels of mRNA before and after gastric bypass.

Conclusions

This is the first study reporting global DNA methylation profiling of adipose tissue before and after gastric bypass and associated weight loss. It provides a strong basis for future work and offers additional evidence for the role of DNA methylation of adipose tissue in obesity.

Comments

Reproduced with permission of BioMed Central. Genome Biology.

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.

Peer Reviewed

1

Open Access

1

Global methylation profile of subcutaneous abdominal adipose and omentum (as Figure 1 ) alongside 15 different healthy tissues.pdf (13 kB)
Global methylation profile of subcutaneous abdominal adipose and omentum (as Figure 1 ) alongside 15 different healthy tissues

Annotated data.xls (836 kB)
Annotated data for the 3,601 differentially methylated CpG sites passing Bonferroni correction in the analysis of subcutaneous adipose before and after weight loss.

List of DMRs mapping to 162 annotated loci identified in subcutaneous adipose tissue.xlsx (18 kB)
List of DMRs mapping to 162 annotated loci identified in subcutaneous adipose tissue

Correlations between changes in DNA methylation and clinical trait in subcutaneous adipose.xlsx (15 kB)
Correlations between changes in DNA methylation and clinical trait in subcutaneous adipose

Correlations for the comparison of 450 K array data with pyrosequence analysis for 15 CpG sites in the subcutaneous adipose samples.pdf (21 kB)
Correlations for the comparison of 450 K array data with pyrosequence analysis for 15 CpG sites in the subcutaneous adipose samples.

DNA methylation data obtained from the pyrosequence analysis of subcutaneous adipose in 18 women and nine men before and after weight loss.xls (46 kB)
DNA methylation data obtained from the pyrosequence analysis of subcutaneous adipose in 18 women and nine men before and after weight loss

DNA methylation data obtained from the pyrosequence analysis of omentum in 17 women and five men before and after weight loss.xls (36 kB)
DNA methylation data obtained from the pyrosequence analysis of omentum in 17 women and five men before and after weight loss

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