Abstract
Metabolic syndrome (MetS) has been postulated to increase the risk for type 2 diabetes, cardiovascular disease and cancer. Adipose tissue (AT) plays an important role in metabolic homeostasis, and AT dysfunction has an active role in metabolic diseases. MetS is closely related to lifestyle and environmental factors. Epigenetics has emerged as an interesting landscape to evaluate the possible interconnection between AT and metabolic disease, since it can be modulated by environmental factors and metabolic status. The aim of this study was to determine whether MetS has an impact on the global DNA methylation pattern and the DNA methylation of several genes related to adipogenesis (PPARG, PPARA), lipid metabolism (RXRA, SREBF2, SREBF1, SCD, LPL, LXRb), and inflammation (LRP1 C3, LEP and TNF) in visceral adipose tissue. LPL and TNF DNA methylation values were significantly different in the control-case comparisons, with higher and lower methylation respectively in the MetS group. Negative correlations were found between global DNA methylation (measured by LINE-1 methylation levels) and the metabolic deterioration and glucose levels. There were associations among variables of MetS, BMI, and HOMA-IR with DNA methylation at several CpG positions for the studied genes. In particular, there was a strong positive association between serum triglyceride levels (TG) with PPARA and LPL methylation levels. TNF methylation was negatively associated with the metabolic worsening and could be an important factor in preventing MetS occurrence according to logistic regression analysis. Therefore, global DNA methylation and methylation at specific genes related to adipogenesis, lipid metabolism and inflammation are related to the etiology of MetS and might explain in part some of the features associated to metabolic disorders.
Highlights
Metabolic syndrome (MetS) is a cluster of metabolic alterations which altogether increase the risk of suffering diabetes, cardiovascular disease and cancer [1,2]
MetS patients showed a clear metabolic deterioration, with higher body mass index (BMI), waist circumference, glucose, insulin, homeostatic model assessment of insulin resistance (HOMA-IR), TG, total cholesterol, low-density lipoprotein cholesterol (LDL-c), apolipoprotein B (ApoB), systolic blood pressure (SBP), diastolic blood pressure (DBP) and leptin; and lower levels of high-density lipoprotein cholesterol (HDL-c) and adiponectin compared to the Non-MetS group (Table 1)
We provide data supporting the idea that global DNA methylation and methylation at specific genes related to adipogenesis, lipid metabolism and inflammation in visceral adipose tissue (VAT) are related to the etiology of MetS
Summary
Metabolic syndrome (MetS) is a cluster of metabolic alterations which altogether increase the risk of suffering diabetes, cardiovascular disease and cancer [1,2]. These metabolic risk factors include high glucose, TG, and blood pressure, low HDL cholesterol (HDL-c) and greater waist circumference [1]. CpG islands (CpGi) are regions composed of a high incidence of repetitions in CpG di-nucleotides inside the genome These CpGi are usually located in or near gene promoters and are usually hypo-methylated, while gene bodies and other intergenic regions are usually hypermethylated [4]. This hypomethylation at CpG promoter regions assures that the transcription starts at the beginning of the gene, avoiding truncated transcripts [5,6]
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