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Validation of differential methylation at specific loci in adipose tissue before and after gastric bypass and the major weight loss associated with it

D Macartney-Coxson*, M Benton, A Johnstone and R S Stubbs

Objective: Type-2 diabetes and obesity are diseases of epidemic proportions.

Gastric bypass surgery results in major weight-loss and in many cases substantial  amelioration of insulin resistance and type-2 diabetes. Using gastric bypass as a model system we have identified differentially methylated loci in adipose tissue before and after surgery. We wish to validate a number of these loci as a first step towards understanding their significance in disease.

Background: We previously investigated DNA methylation, in two different adipose tissues subcutaneous adipose and omentum before and after gastric bypass and associated weight-loss using the high-density Illumina 450K platform. A paired analyses before surgery andafter subsequent weight-loss revealed significant differential methylation (Bonferroni p<1x10-7) in subcutaneous adipose and omentum at 3601 and 15 cytosine guanine dinucleotides (CpGs) respectively. This differential methylation was observed within obesity candidate genes, genomic regions associated with obesity, non-coding RNA loci and genes involved in epigenetic regulation and development. We sought WMRF funding to validate a number of these differentially methylated loci using an independent technique, pyrosequencing.

Validation of differential methylation at specific loci in adipose tissue before and after gastric bypass and the major weight loss associated with it

 
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