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Background  Epigenetic mechanisms may be involved in the regulation of genes found to be differentially expressed in the visceral adipose tissue (VAT) of severely obese subjects with (MetS+) versus without (MetS-) metabolic syndrome (MetS). Long interspersed nuclear element 1 ( LINE-1 ) elements DNA methylation levels (%meth) in blood, a marker of global DNA methylation, have recently been associated with fasting glucose, blood lipids, heart diseases and stroke.    Aim  To test whether  LINE-1 %meth levels in VAT are associated with MetS phenotypes and whether they can predict MetS risk in severely obese individuals.    Methods  DNA was extracted from VAT of 34 men (MetS-:  n  = 14, MetS+:  n  = 20) and 152 premenopausal women (MetS-:  n  = 84; MetS+:  n  = 68) undergoing biliopancreatic diversion for the treatment of obesity.  LINE-1 %meth levels were assessed by pyrosequencing of sodium bisulfite-treated DNA.    Results  The mean  LINE-1 %meth in VAT was of 75.8% (SD = 3.0%). Multiple linear regression analyses revealed that  LINE-1 %meth was negatively associated with fasting glucose levels (β = -0.04;  P  = 0.03), diastolic blood pressure (β =  -0.65;  P  = 0.03) and MetS status (β = -0.04;  P  = 0.004) after adjustments for the effects of age, sex, waist circumference (except for MetS status) and smoking. While dividing subjects into quartiles based on their  LINE-1 %meth (Q1 to Q4: lower %meth to higher %meth levels), greater risk were observed in the first (Q1: odds ratio (OR) = 4.37,  P  = 0.004) and the second (Q2: OR = 4.76,  P  = 0.002) quartiles compared to Q4 (1.00) when adjusting for age, sex and smoking.    Conclusions  These results suggest that lower global DNA methylation, assessed by  LINE-1  repetitive elements methylation analysis, would be associated with a greater risk for MetS in the presence of obesity.

LINE-1 methylation in visceral adipose tissue of severely obese individuals is associated with metabolic syndrome status and related phenotypes