DNA methylation of tumor necrosis factor‐α, monocyte chemoattractant protein‐1, and adiponectin genes in visceral adipose tissue is related to type 2 diabetes in the Xinjiang Uygur population

Zhang, Jun; Wang, Cuizhe; Ha, Xiaodan; Li, Wei; Xu, Peng; Gu, Yajuan; Wang, Tingting; Wang, Yan; Xie, Jingui

doi:10.1111/1753-0407.12478

Cited by 14 publications

(14 citation statements)

References 18 publications

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“…Aerobic exercise did not alter the DNA methylation or mRNA expression of either IL6 or TNF. The epigenetic impact of exercise on inflammatory cytokines is relatively unknown, however, several studies have indicated a role for cytokine DNA methylation in inflammatory disease [34][35][36][37]. Although no association between TNF DNA methylation and mRNA expression was detected in the present study, n-3 PUFAs have previously been demonstrated to reverse the epigenetic changes observed with inflammation in skeletal muscle cells.…”

Section: Discussioncontrasting

confidence: 81%

“…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.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2019

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Lifestyle interventions, including exercise and dietary supplementation, can modify DNA methylation and exert health benefits; however, the underlying mechanisms are poorly understood. Here we investigated the impact of acute aerobic exercise and the supplementation of omega-3 polyunsaturated fatty acids (n-3 PUFA) and extra virgin olive oil (EVOO) on global and gene-specific (PPARGC1A, IL6 and TNF) DNA methylation, and DNMT mRNA expression in leukocytes of diseasefree individuals. Eight trained male cyclists completed an exercise test before and after a four-week supplementation of n-3 PUFA and EVOO in a double-blind, randomised, repeated measures design. Exercise triggered global hypomethylation (Pre 79.2%; Post 78.7%; p = 0.008), alongside, hypomethylation (Pre 6.9%; Post 6.3%; p < 0.001) and increased mRNA expression of PPARGC1A (p < 0.001). Associations between PPARGC1A methylation and exercise performance were also detected. An interaction between supplement and trial was detected for a single CpG of IL6 indicating increased DNA methylation following n-3 PUFA and decreased methylation following EVOO (p = 0.038). Global and gene-specific DNA methylation associated with markers of inflammation and oxidative stress. The supplementation of EVOO reduced DNMT1 mRNA expression compared to n-3 PUFA supplementation (p = 0.048), whereas, DNMT3a (p = 0.018) and DNMT3b (p = 0.046) mRNA expression were decreased following exercise. In conclusion, we demonstrate that acute exercise and dietary supplementation of n-3 PUFAs and EVOO induce DNA methylation changes in leukocytes, potentially via the modulation of DNMT mRNA expression. Future studies are required to further elucidate the impact of lifestyle interventions on DNA methylation. ARTICLE HISTORY

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Section: Discussioncontrasting

confidence: 81%

Section: Introductionmentioning

confidence: 99%

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

et al. 2019

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“…Among several factors, a very recent population based study carried out in the USA confirmed that obesity, diabetes mellitus, family history of other malignancy, and smoking independently increase the odds ratio for the occurrence of colorectal cancer [83]. Inflammatory cytokines appear to play a key role in linking obesity and colorectal carcinogenesis particularly so for IL-6 and tumor necrosis factor-α [84,85]; a recent study also describing IL-13 as a potential factor involved in the development of obesity-related colon cancer onset [86]. As it was the case for colon rectal cancer, also for the gastro-esophageal cancer a positive relationship between abdominal obesity and cancer occurrence has been described.…”

Section: Gi Cancermentioning

confidence: 99%

Role of Overweight and Obesity in Gastrointestinal Disease

et al. 2019

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The prevalence of obesity is increasing worldwide, leading to a severe impairment of overall health. Actually, obesity has been associated with several pathological conditions, causing an excess overall mortality. In particular, overweight and obesity are well known risk factors for a variety of gastrointestinal (GI) disorders i.e., functional GI disorders as well as, inflammatory bowel disease (IBD), pancreatitis, and GI cancer. The aim of the present review is to summarize the potential role of overweight and obesity in GI disease with particular focus on plausible biological mechanisms that could explain the association between obesity and GI disease based on the most recent evidence in the literature.

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“…Previous studies addressing obesity-related colorectal tumorigenesis focused on the function of several cytokines, including IL-6 and tumor necrosis factor-α. 15,16 However, these previous studies provided information on the role of individual cytokines of interest, and identification of the dominant cytokines involved in CRC tumorigenesis and their dynamic effects on carcinogenesis under obese conditions remain to be elucidated. A high-throughput screening analysis of related cytokines and subsequent mechanistic analysis are needed to address this problem.…”

Section: Introductionmentioning

confidence: 99%

Interleukin‐13 and its signaling pathway is associated with obesity‐related colorectal tumorigenesis

et al. 2019

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The incidence of colorectal cancer (CRC) has been on the rise, which is linked to the increasing prevalence of obesity, based on global epidemiological evidence. Although chronic inflammation is implicated in tumor development, the mechanisms underlying obesity‐associated CRC remain unknown. Here, we sought to identify the inflammatory cytokines and their roles in obesity‐related colorectal tumorigenesis using cytokine array analyses in a mouse model. Colorectal tumorigenesis was induced through i.p. injection of azoxymethane once a week for 6 weeks in 6‐week‐old female WT C57Black/6J mice and the obesity diabetes model mouse KK/TaJcl, KK‐Ay/TaJcl. The formation of aberrant crypt foci and colorectal tumors were more frequent in obese mice compared with WT mice, and both serum interleukin (IL)‐13 and IL‐13 receptor (R) expression in the normal intestinal mucosal epithelium were significantly increased in the obese mice. Furthermore, addition of IL‐13 to a human CRC cell line and a human colon organoid culture altered the phenotype of intestinal epithelial cells. Knockdown experiments further revealed that IL‐13Rα1 dominantly induced mucosal proliferation. Collectively, These results suggest an association between anti‐inflammatory cytokines and colorectal carcinogenesis, and provide new research directions for cancer prevention strategies. In particular, inflammation provoked by obesity, notably by increased expression of the cytokine IL‐13, could play an important role in the carcinogenesis of obesity‐related CRC.

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DNA methylation of tumor necrosis factor‐α, monocyte chemoattractant protein‐1, and adiponectin genes in visceral adipose tissue is related to type 2 diabetes in the Xinjiang Uygur population

Abstract: Lower ADIPOQ and higher TNF and MCP1 mRNA expression in visceral adipose tissue may be correlated with obesity and T2DM in the Uygur population. Promoter DNA methylation affects expression of ADIPOQ and TNF.

Cited by 14 publications

References 18 publications

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

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

Role of Overweight and Obesity in Gastrointestinal Disease

Interleukin‐13 and its signaling pathway is associated with obesity‐related colorectal tumorigenesis

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