Dataset Information

Epigenetic silencing of the ANKRD26 gene correlates to the pro-inflammatory profile and increased cardio-metabolic risk factors in human obesity.

ABSTRACT: BACKGROUND:Obesity is a major worldwide threat to human health. Increasing evidence indicates that epigenetic modifications have a major impact on the natural history of this disorder. Ankyrin Repeat Domain 26 (Ankrd26) is involved in the development of both obesity and diabetes in mice and is modulated by environmentally induced epigenetic modifications. This study aims at investigating whether impaired ANKRD26 gene expression and methylation occur in human obesity and whether they correlate to the phenotype of these subjects. RESULTS:We found that downregulation of ANKRD26 mRNA and hyper-methylation of a specific region of the ANKRD26 promoter, embedding the CpG dinucleotides - 689, - 659, and - 651?bp, occur in peripheral blood leukocytes from obese compared with the lean subjects. ANKRD26 gene expression correlates inversely to the percentage of DNA methylation at these 3 CpG sites. Luciferase assays reveal a cause-effect relationship between DNA methylation at the 3 CpG sites and ANKRD26 gene expression. Finally, both ANKRD26 mRNA levels and CpG methylation correlate to body mass index and to the pro-inflammatory status and the increased cardio-metabolic risk factors of these same subjects. CONCLUSION:Downregulation of the ANKRD26 gene and hyper-methylation at specific CpGs of its promoter are common abnormalities in obese patients. These changes correlate to the pro-inflammatory profile and the cardio-metabolic risk factors of the obese individuals, indicating that, in humans, they mark adverse health outcomes.

SUBMITTER: Desiderio A

PROVIDER: S-EPMC6894277 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Epigenetic silencing of the ANKRD26 gene correlates to the pro-inflammatory profile and increased cardio-metabolic risk factors in human obesity.

Desiderio Antonella A Longo Michele M Parrillo Luca L Campitelli Michele M Cacace Giuseppe G de Simone Sonia S Spinelli Rosa R Zatterale Federica F Cabaro Serena S Dolce Pasquale P Formisano Pietro P Milone Marco M Miele Claudia C Beguinot Francesco F Raciti Gregory A GA

Clinical epigenetics 20191204 1

<h4>Background</h4>Obesity is a major worldwide threat to human health. Increasing evidence indicates that epigenetic modifications have a major impact on the natural history of this disorder. Ankyrin Repeat Domain 26 (Ankrd26) is involved in the development of both obesity and diabetes in mice and is modulated by environmentally induced epigenetic modifications. This study aims at investigating whether impaired ANKRD26 gene expression and methylation occur in human obesity and whether they corr ...[more]

PMID: 31801613

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Project description:BACKGROUND:Suicide risk assessments are often challenging for clinicians, and therefore, biological markers are warranted as guiding tools in these assessments. Suicidal patients display increased cytokine levels in peripheral blood, although the composite inflammatory profile in the subjects is still unknown. It is also not yet established whether certain inflammatory changes are specific to suicidal subjects. To address this, we measured 45 immunobiological factors in peripheral blood and identified the biological profiles associated with cross-diagnostic suicide risk and depression, respectively. METHODS:Sixty-six women with mood and anxiety disorders underwent computerized adaptive testing for mental health, assessing depression and suicide risk. Weighted correlation network analysis was used to uncover system level associations between suicide risk, depression, and the immunobiological factors in plasma. Secondary regression models were used to establish the sensitivity of the results to potential confounders, including age, body mass index (BMI), treatment and symptoms of depression and anxiety. RESULTS:The biological profile of patients assessed to be at increased suicide risk differed from that associated with depression. At the system level, a biological cluster containing increased levels of interleukin-6, lymphocytes, monocytes, white blood cell count and polymorphonuclear leukocyte count significantly impacted suicide risk, with the latter two inferring the strongest influence. The cytokine interleukin-8 was independently and negatively associated with increased suicide risk. The results remained after adjusting for confounders. LIMITATIONS:This study is cross-sectional and not designed to prove causality. DISCUSSION:A unique immunobiological profile was linked to increased suicide risk. The profile was different from that observed in patients with depressive symptoms, and indicates that granulocyte mediated biological mechanisms could be activated in patients at risk for suicide.

Project description:BackgroundObesity is a major risk factor for dysglycemic disorders, including type 2 diabetes (T2D). However, there is wide phenotypic variation in metabolic profiles. Tissue-specific epigenetic modifications could be partially accountable for the observed phenotypic variability.ScopeThe aim of this systematic review was to summarize the available data on epigenetic signatures in human adipose tissue (AT) that characterize overweight or obesity-related insulin resistance (IR) and dysglycemia states and to identify potential underlying mechanisms through the use of unbiased bioinformatics approaches.MethodsOriginal data published in the last decade concerning the comparison of epigenetic marks in human AT of individuals with metabolically unhealthy overweight/obesity (MUHO) versus normal weight individuals or individuals with metabolically healthy overweight/obesity (MHO) was assessed. Furthermore, association of these epigenetic marks with IR/dysglycemic traits, including T2D, was compiled.ResultsWe catalogued more than two thousand differentially methylated regions (DMRs; above the cut-off of 5%) in the AT of individuals with MUHO compared to individuals with MHO. These DNA methylation changes were less likely to occur around the promoter regions and were enriched at loci implicated in intracellular signaling (signal transduction mediated by small GTPases, ERK1/2 signaling and intracellular trafficking). We also identified a network of seven transcription factors that may play an important role in targeting DNA methylation changes to specific genes in the AT of subjects with MUHO, contributing to the pathogeny of obesity-related IR/T2D. Furthermore, we found differentially methylated CpG sites at 8 genes that were present in AT and whole blood, suggesting that DMRs in whole blood could be potentially used as accessible biomarkers of MUHO.ConclusionsThe overall evidence linking epigenetic alterations in key tissues such AT to metabolic complications in human obesity is still very limited, highlighting the need for further studies, particularly those focusing on epigenetic marks other than DNA methylation. Our initial analysis suggests that DNA methylation patterns can potentially discriminate between MUHO from MHO and provide new clues into why some people with obesity are less susceptible to dysglycemia. Identifying AT-specific epigenetic targets could also lead to novel approaches to modify the progression of individuals with obesity towards metabolic disease.Systematic review registrationPROSPERO, identifier CRD42021227237.

Dataset Information

Epigenetic silencing of the ANKRD26 gene correlates to the pro-inflammatory profile and increased cardio-metabolic risk factors in human obesity.

Publications

Epigenetic silencing of the ANKRD26 gene correlates to the pro-inflammatory profile and increased cardio-metabolic risk factors in human obesity.

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