Visceral adipose tissue DNA methylation at dipeptidyl peptidase‐4 gene locus is associated with gene expression and plasma lipid levels in severe obesity

Abstract

Dipeptidyl peptidase‐4 (DPP4) is overexpressed in visceral adipose tissue of severely obese subjects with the metabolic syndrome (MS) as compared to those without MS.AimTo test whether methylation of DPP4 is associated with DPP4 mRNA levels and MS‐phenotypes.MethodsGreater omentum fat tissue DNA was extracted in 92 severely obese women undergoing biliopancreatic derivation to treat morbid obesity. Women were premenopausal, non‐diabetic and not taking medications to treat MS features. Cytosine methylation levels (%) in DPP4 CpG island (Human build 36.3; chr2: 162638045‐162639319 reverse strand) was assessed by pyrosequencing of sodium bisulfite treated DNA.ResultsMean methylation levels of combined CpG sites no.94–102 (%Meth) were calculated. The %Meth correlated negatively with DPP4 mRNA levels (r=0.25, p<0.05). Subjects with %Meth corresponding to the second tertile had lower total‐ and LDL‐cholesterol levels (PANOVA<0.05; adjusted for age, smoking, body mass index).ConclusionsIn visceral adipose tissue of severely obese women, lower methylation levels of specific DPP4 CpG sites were associated with higher mRNA levels. Methylation levels were also associated with blood lipids.Grant Funding Source: Canadian Institutes of Health Research