Increased Methylation of Interleukin 6 Gene Is Associated with Obesity in Korean Women

Abstract

Obesity is the fifth leading risk for death globally, and a significant challenge to global health. It is a common, complex, non-malignant disease and develops due to interactions between the genes and the environment. DNA methylation can act as a downstream effector of environmental signals; analysis of this process therefore holds substantial promise for identifying mechanisms through which genetic and environmental factors jointly contribute to disease risk. To assess the effects of excessive weight and obesity on gene-specific methylation levels of promoter regions, we determined the methylation status of four genes involved in inflammation and oxidative stress [interleukin 6 (IL6), tumor necrosis factor α (TNFα), mitochondrial transcription factor A (TFAM), and glucose transport 4 (GLUT4)] in blood cell-derived DNA from healthy women volunteers with a range of body mass indices (BMIs) by methylation-specific PCR. Interestingly, the samples from obese individuals (BMI ≥ 30 kg/m2) showed significantly increased hypermethylation for IL6 gene compared to normal weight (BMI < 23 kg/m2) and overweight samples (23 kg/m2 ≤ BMI < 30 kg/m2) (P = 0.034 and P = 0.026). However, there was no statistically significant difference in promoter methylation of the other 3 genes between each group. These findings suggest that aberrant DNA methylation of IL6 gene promoter may play an important role in the etiology and pathogenesis of obesity and IL6 methylation could be used as molecular biomarker for obesity risk assessment. Further studies are required to elucidate the potential mechanisms underlying this relationship.

Low Oxygen Consumption is Related to a Hypomethylation and an Increased Secretion of IL-6 in Obese Subjects with Sleep Apnea-Hypopnea Syndrome

“…Furthermore, recent studies have demonstrated a relationship between DNA methylation and metabolic diseases, such as obesity [21]. Therefore, the methylation levels of the promoter region in the following genes IL6 , LINE1 , SERPINE1, and TNF , previously linked with this type of pathological conditions [21,31,32,33,37,38,39], were evaluated in obese subjects with SAHS, in order to examine the molecular links between resting oxygen consumption and chronic diseases. Methylation levels of IL6 and SERPINE1 were positively associated with FFM.…”

“…In addition, obesity has been associated with increased DNA methylation levels of IL6 gene in PBC from women [39]. Moreover, a genome-wide association study performed in European obese subjects established a positive association between BMI and hypoxia-inducible 3A locus methylation in PBC and adipose tissue, suggesting a possible role of oxygen in the response to weight gain [23].…”

“…Besides, some studies have investigated the relation between methylation pattern of genes with obesity, metabolic disturbances, and aging [27,28,35,36]. For instance, this link has been shown in inflammatory markers such as serpin peptidase inhibitor, clade E member 1 ( SERPINE1 ) encoding plasminogen activator inhibitor 1 [37]; tumor necrosis factor ( TNF ) [38] and interleukin 6 ( IL6 ) [21,39], among others. Therefore, the aim of the present study was to analyze the influence of resting oxygen consumption on global and gene promoter DNA methylation and protein secretion of inflammatory markers in PBC from obese subjects with SAHS.…”

Impact of aerobic exercise and fatty acid supplementation on global and gene-specific DNA methylation

“…Increases in markers of oxidative stress and circulating levels of inflammatory cytokines, such as IL-6 and TNFa, have been shown to alter the expression of DNA methyltransferases (DNMTs) [28][29][30][31][32] and influence DNA methylation patterns [11,33]. DNA methylation of inflammatory cytokines have been associated with various inflammatory diseases including IL6 with Rheumatoid Arthritis [34] and obesity [35]; TNF DNA methylation with type 2 diabetes [36] and Alzheimer's disease [37]. Despite increased circulating levels of inflammatory cytokines post-exercise [14,23], the impact of exercise on the DNA methylation of genes encoding inflammatory cytokines such as IL6 and TNF remains unknown.…”

Inflammation and Oxidative Stress: Critical Role for Metabolic Syndrome

“…Authors believe that aberrant DNA methylation of IL6 gene promoter may play an important role in the etiology and pathogenesis of obesity and IL6 methylation could be used as molecular biomarker for obesity risk assessment because DNA methylation can act as a downstream effector of environmental signals [24]. Among the various nuclear receptors, peroxisome proliferator-activated receptor γ promotes the transcription of adiponectin and antioxidative enzymes, whereas mineralocorticoid receptor mediates the effects of aldosterone and glucocorticoid to induce oxidative stress in adipocytes.…”