Background: The dipeptidyl peptidase-4 (DPP4) enzyme is a novel adipokine potentially involved in the\r\ndevelopment of the metabolic syndrome (MetS). Previous observations demonstrated higher visceral adipose tissue\r\n(VAT) DPP4 gene expression in non-diabetic severely obese men with (MetS+) vs. without (MetS-) MetS. DPP4\r\nmRNA abundance in VAT correlated also with CpG site methylation levels (%Meth) localized within and near its\r\nexon 2 (CpG94 to CpG102) in non-diabetic severely obese women, regardless of their MetS status. The actual study\r\ntested whether DPP4 %Meth levels in VAT are different between MetS- and MetS+ non-diabetic severely obese\r\nsubjects, whether variable metabolic and plasma lipid profiles are observed between DPP4 %Meth quartiles, and\r\nwhether correlation exists in DPP4 %Meth levels between VAT and white blood cells (WBCs).\r\nMethods: DNA was extracted from the VAT of 26 men (MetS-: n=12, MetS+: n=14) and 79 women (MetS-: n=60;\r\nMetS+: n=19), as well as from WBCs in a sub-sample of 17 women (MetS-: n=9; MetS+: n=8). The %Meth levels of\r\nCpG94 to CpG102 were assessed by pyrosequencing of sodium bisulfite-treated DNA. ANOVA analyses were used to\r\ncompare the %Meth of CpGs between MetS- and MetS+ groups, and to compare the metabolic phenotype and\r\nplasma lipid levels between methylation quartiles. Pearson correlation coefficient analyses were computed to test\r\nthe relationship between VAT and WBCs CpG94-102 %Meth levels.\r\nResults: No difference was observed in CpG94-102 %Meth levels between MetS- and MetS+ subjects in VAT\r\n(P=0.67), but individuals categorized into CpG94-102 %Meth quartiles had variable plasma total-cholesterol\r\nconcentrations (P=0.04). The %Meth levels of four CpGs in VAT were significantly correlated with those observed in\r\nWBCs (r=0.55-0.59, P=0.03).\r\nConclusions: This study demonstrated that %Meth of CpGs localized within and near the exon 2 of the DPP4 gene\r\nin VAT are not associated with MetS status. The actual study also revealed an association between the %Meth of\r\nthis locus with plasma total-cholesterol in severe obesity, which suggests a link between the DPP4 gene and\r\nplasma lipid levels.
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