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

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.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.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.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.Accumulation of fat preferentially in the abdominal cavity is frequently associated with clustering of metabolic and inflammatory alterations, often referred to as metabolic syndrome (MetS) [1,2]. However, there exists a large heterogeneity in the development of these metabolic complications among obese individuals [3,4], which may partly be explained by impairment of adipose tissue function [5,6]. Previous studies observed differential gene expression patterns in visceral adipose tissue (VAT) of ‘metabolically healthy’ vs ‘metabolically unhealthy’ obese individuals [7-9]. It is thus possible that some of these differentially expressed genes may be functionally related to VAT dysf