Epigenome-wide methylation differences in a group of lean and obese women – A HUNT Study

Kvaløy, Kirsti; Page, Christian M.; Holmen, Turid Lingaas

doi:10.1038/s41598-018-34003-8

Cited by 29 publications

(23 citation statements)

References 65 publications

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“…However modest, these changes illustrated how the exposures, to which the cell types involved in the development of atherosclerosis and in thrombus formation are subjected, modify the molecular phenotypes. Similar results have previously been reported for whole blood cell DNA methylation 54 . With the above exception in macrophages, we found that the two extreme phenotype groups were, as expected, more similar to each other than to the lean group overall, again reflecting the underlying AT dysfunction.…”

Section: Resultssupporting

confidence: 91%

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Transcriptional, epigenetic and metabolic signatures in cardiometabolic syndrome defined by extreme phenotypes

Seyres¹,

Cabassi

Lambourne³

et al. 2020

Preprint

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Providing a molecular characterisation of cardiometabolic syndrome (CMS) could improve our understanding of its pathogenesis and pathophysiology, and provide a step toward the development of better treatments. To this end, we performed a deep phenotyping analysis of 185 blood donors, 10 obese, and 10 lipodystrophy patients.We analysed transcriptomes and epigenomes of monocytes, neutrophils, macrophages and platelets. Additionally, plasma metabolites including lipids and biochemistry measurements were quantified.Multi-omics integration of this data allowed us to identify combinations of features related to patient status and to order the donor population according to their molecular similarity to patients. We also performed differential analyses on epigenomic, transcriptomic and plasma proteomic data collected from obese individuals before and six months after bariatric surgery. These analyses revealed a pattern of abnormal activation of immune cells in obese individuals and lipodystrophy patients, which was partially reverted six months after bariatric surgery.

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Section: Resultssupporting

confidence: 91%

“…Similar results have previously been reported for whole blood cell DNA methylation (Kvaløy, Page and Holmen, 2018), while more extensive changes have been observed in adipose tissue (Ling and Rönn, 2019).…”

Section: Transcriptional and Epigenetic Signaturessupporting

confidence: 90%

Transcriptional, epigenetic and metabolic signatures in cardiometabolic syndrome defined by extreme phenotypes

Seyres¹,

Cabassi

Lambourne³

et al. 2020

Preprint

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show abstract

“…Epigenome-wide association studies have reported global DNA hypomethylation and the differential methylation of some inflammatory and adipogenesis genes in peripheral blood cells of obese individuals compared with their lean counterparts [53][54][55]. Yet, it is critical to analyze tissue-specific DNA methylation profiles instead of testing easily accessible blood samples especially after differential DNA methylation patterns were noted among various tissues in previous studies [56].…”

Section: Discussionmentioning

confidence: 99%

HIF1α/TET1 Pathway Mediates Hypoxia-Induced Adipocytokine Promoter Hypomethylation in Human Adipocytes

Ali

Phillips

Mahmoud

2020

Cells

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Obesity is associated with the accumulation of dysfunctional adipose tissue that secretes several pro-inflammatory cytokines (adipocytokines). Recent studies have presented evidence that adipose tissues in obese individuals and animal models are hypoxic, which may result in upregulation and stabilization of the hypoxia inducible factor HIF1α. Epigenetic mechanisms such as DNA methylation enable the body to respond to microenvironmental changes such as hypoxia and may represent a mechanistic link between obesity-associated hypoxia and upregulated inflammatory adipocytokines. The purpose of this study was to investigate the role of hypoxia in modifying adipocytokine DNA methylation and subsequently adipocytokine expression. We suggested that this mechanism is mediated via the DNA demethylase, ten-eleven translocation-1 (TET1), transcription of which has been shown to be induced by HIF1α. To this end, we studied the effect of hypoxia (2% O2) in differentiated subcutaneous human adipocytes in the presence or absence of HIF1α stabilizer (Dimethyloxalylglycine (DMOG), 500 μM), HIF1α inhibitor (methyl 3-[[2-[4-(2-adamantyl) phenoxy] acetyl] amino]-4-hydroxybenzoate, 30 μM), or TET1-specific siRNA. Subjecting the adipocytes to hypoxia significantly induced HIF1α and TET1 protein levels. Moreover, hypoxia induced global hydroxymethylation, reduced adipocytokine DNA promoter methylation, and induced adipocytokine expression. These effects were abolished by either HIF1α inhibitor or TET1 gene silencing. The major hypoxia-responsive adipocytokines were leptin, interleukin-1 (IL6), IL1β, tumor necrosis factor α (TNFα), and interferon γ (IFNγ). Overall, these data demonstrate an activation of the hydroxymethylation pathway mediated by TET1. This pathway contributes to promoter hypomethylation and gene upregulation of the inflammatory adipocytokines in adipocytes in response to hypoxia.

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“…Genome wide association studies has led to the discovery of novel obesity susceptibility loci [ 33 ]. Moreover, studies on comparative genetics, heritability analysis and DNA methylation show similarities in genomic regions of interest for studying obesity [ [34] , [35] , [36] ].…”

Section: Discussionmentioning

confidence: 99%

Circulating miR-216a as a biomarker of metabolic alterations and obesity in women

Vonhögen

Mohseni

Winkens

et al. 2020

Non-coding RNA Research

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Obesity leads to an amplified risk of disease and contributes to the occurrence of type 2 diabetes, fatty liver disease, coronary heart disease, stroke, chronic kidney disease and various types of cancer. MicroRNAs (miRNAs), small non-coding RNA molecules of 20–25 nucleotides, can remain stable in plasma and have been studied as potential (predictive) biomarkers for obesity and related metabolic disorders. The aim of this study was to identify circulating miRNAs as biomarkers for obesity status and metabolic alterations in women. Circulating miR-216a and miR-155–5p were selected by miRNA expression profiling and validated by real time quantitative PCR in a validation cohort of 60 obese women and 60 normal weight-age-matched control women. This was supplemented by correlation analysis of the candidate miRNA and anthropometric variables, blood biochemistry and lipid profile markers. Circulating miR-216a was validated as a biomarker of obesity status with significantly reduced levels in obese women. Interestingly, this was associated with a negative correlation between the plasma miR-216a content and body mass index (BMI), waist circumference, mean arterial pressure (MAP), triglycerides, ratio of total cholesterol/high density lipoprotein (HDL)-cholesterol and high sensitivity-C reactive protein (hs-CRP).Taken together, we provide evidence for an abnormally expressed circulating miRNA, miR-216a, with additive value as a predictive marker for obesity that correlates with metabolic alterations presented by lipid profile and inflammatory markers.

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Epigenome-wide methylation differences in a group of lean and obese women – A HUNT Study

Cited by 29 publications

References 65 publications

Transcriptional, epigenetic and metabolic signatures in cardiometabolic syndrome defined by extreme phenotypes

Transcriptional, epigenetic and metabolic signatures in cardiometabolic syndrome defined by extreme phenotypes

HIF1α/TET1 Pathway Mediates Hypoxia-Induced Adipocytokine Promoter Hypomethylation in Human Adipocytes

Circulating miR-216a as a biomarker of metabolic alterations and obesity in women

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