scholarly journals DNA Methylation in the Adipose Tissue and Whole Blood of Agent Orange-exposed Operation Ranch Hand Veterans

2020 ◽  
Author(s):  
Matthew Rae Rytel ◽  
Rondi Butler ◽  
Melissa Eliot ◽  
Joseph M. Braun ◽  
E. Andres Houseman ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Adipose Tissue ◽  
Vietnam War ◽  
Air Force ◽  
Whole Blood ◽  
Body Burden ◽  
Serum Levels ◽  
Agent Orange ◽  
Health Study ◽  
The Impact

Abstract BackgroundBetween 1962 and 1971, the US Air Force sprayed Agent Orange across Vietnam, exposing many soldiers to this dioxin-containing herbicide. Several negative health outcomes have been linked to Agent Orange exposure, but data is lacking on the effects this chemical has on the genome. Therefore, we sought to characterize the impact of Agent Orange exposure on DNA methylation in the whole blood and adipose tissue of veterans enrolled in the Air Force Health Study (AFHS). MethodsWe received adipose tissue (n=37) and whole blood (n=42) from veterans in the AFHS. Study participants were grouped as having low, moderate, or high TCDD body burden based on their previously measured serum levels of dioxin. DNA methylation was assessed using the Illumina 450K platform.ResultsEpigenome-wide analysis indicated that there were no FDR-significantly methylated CpGs in either tissue with TCDD burden. However, 3 CpGs in the adipose tissue (contained within SLC9A3, LYNX1, and TNRC18) were marginally significantly (q<0.1) hypomethylated, and 1 CpG in whole blood (contained within PTPRN2) was marginally significantly (q<0.1) hypermethylated with high TCDD burden. Analysis for differentially methylated DNA regions yielded SLC9A3, among other regions in adipose tissue, to be significantly differentially methylated with higher TCDD burden. Comparing whole blood data to a study of dioxin exposed adults from Alabama identified a CpG within the gene SMO that was hypomethylated with dioxin exposure in both studies. ConclusionWe found limited evidence of dioxin associated DNA methylation in adipose tissue and whole blood in this pilot study of Vietnam War veterans. Nevertheless, loci in the genes of SLC9A3 in adipose tissue, and PTPRN2 and SMO in whole blood, should be included in future exposure analyses.

scholarly journals DNA methylation in the adipose tissue and whole blood of Agent Orange-exposed Operation Ranch Hand veterans: a pilot study

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Matthew R. Rytel ◽  
Rondi Butler ◽  
Melissa Eliot ◽  
Joseph M. Braun ◽  
E. Andres Houseman ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Adipose Tissue ◽  
Pilot Study ◽  
Air Force ◽  
Whole Blood ◽  
Body Burden ◽  
Serum Levels ◽  
Agent Orange ◽  
Health Study ◽  
The Impact

Abstract Background Between 1962 and 1971, the US Air Force sprayed Agent Orange across Vietnam, exposing many soldiers to this dioxin-containing herbicide. Several negative health outcomes have been linked to Agent Orange exposure, but data is lacking on the effects this chemical has on the genome. Therefore, we sought to characterize the impact of Agent Orange exposure on DNA methylation in the whole blood and adipose tissue of veterans enrolled in the Air Force Health Study (AFHS). Methods We received adipose tissue (n = 37) and whole blood (n = 42) from veterans in the AFHS. Study participants were grouped as having low, moderate, or high TCDD body burden based on their previously measured serum levels of dioxin. DNA methylation was assessed using the Illumina 450 K platform. Results Epigenome-wide analysis indicated that there were no FDR-significantly methylated CpGs in either tissue with TCDD burden. However, 3 CpGs in the adipose tissue (contained within SLC9A3, LYNX1, and TNRC18) were marginally significantly (q < 0.1) hypomethylated, and 1 CpG in whole blood (contained within PTPRN2) was marginally significantly (q < 0.1) hypermethylated with high TCDD burden. Analysis for differentially methylated DNA regions yielded SLC9A3, among other regions in adipose tissue, to be significantly differentially methylated with higher TCDD burden. Comparing whole blood data to a study of dioxin exposed adults from Alabama identified a CpG within the gene SMO that was hypomethylated with dioxin exposure in both studies. Conclusion We found limited evidence of dioxin associated DNA methylation in adipose tissue and whole blood in this pilot study of Vietnam War veterans. Nevertheless, loci in the genes of SLC9A3 in adipose tissue, and PTPRN2 and SMO in whole blood, should be included in future exposure analyses.

scholarly journals Serum dioxin and DNA methylation in the sperm of operation ranch hand veterans exposed to Agent Orange

2019 ◽  
Vol 18 (1) ◽  
Author(s):  
Karl T. Kelsey ◽  
Matthew Rytel ◽  
Edward Dere ◽  
Rondi Butler ◽  
Melissa Eliot ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Vietnam War ◽  
Vietnam Veterans ◽  
Agent Orange ◽  
Health Study ◽  
High Exposure ◽  
Adverse Health Outcomes ◽  
Low Exposure ◽  
Dioxin Exposure ◽  
Candidate Loci

Abstract Background Exposure to the herbicide Agent Orange during the Vietnam War was widespread and is associated with numerous adverse health outcomes. A continuing concern of veterans is the possibility that exposure to the dioxin-containing herbicide might induce adverse reproductive outcomes. We sought to assess whether exposure to Agent Orange in Vietnam was associated with changes in DNA methylation in sperm in a subset of Vietnam veterans who participated in the Air Force Health Study (AFHS). Methods We studied 37 members of the AFHS chosen to have no, low, medium or high exposure to Agent Orange, based upon serum dioxin levels obtained during a series of examinations. DNA from stored semen was extracted and DNA methylation assessed on the Illumina 450 K platform. Results Initial epigenome-wide analysis returned no loci that survived control for false discovery. However, the TEAD3 gene had four different CpG sites that showed loss of DNA methylation associated with dioxin exposure. Analysis assessing regional DNA methylation changes revealed 36 gene regions, including the region of the imprinted gene H19 to have altered DNA methylation associated with high exposure compared to the low exposure group. Additional comparison of our data with sperm DNA methylation data from Russian boys exposed to dioxin found an additional 5 loci that were altered in both studies and exhibited a consistent direction of association. Conclusions Studying a small number of sperm samples from veterans enrolled in the AFHS, we did not find evidence of significant epigenome-wide alterations associated with exposure to Agent Orange. However, additional analysis showed that the H19 gene region is altered in the sperm of Agent Orange-exposed Ranch Hand veterans. Our study also replicated several findings of a prior study of dioxin-exposed Russian boys. These results provide additional candidate loci for further investigation and may have implications for the reproductive health of dioxin-exposed individuals.

Serum dioxin levels and sperm DNA methylation age: Findings in Vietnam war veterans exposed to Agent Orange

2020 ◽  
Vol 96 ◽  
pp. 27-35
Author(s):  
Jamaji C. Nwanaji-Enwerem ◽  
Timothy G. Jenkins ◽  
Elena Colicino ◽  
Andres Cardenas ◽  
Andrea A. Baccarelli ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Vietnam War ◽  
Agent Orange ◽  
War Veterans ◽  
Sperm Dna ◽  
Dna Methylation Age ◽  
Vietnam War Veterans ◽  
Sperm Dna Methylation

The Impact of Exercise on DNA Methylation of Genes Associated with Type 2 Diabetes and Obesity in Human Adipose Tissue

2014 ◽  
Vol 10 (01) ◽  
pp. 64 ◽  
Author(s):  
Tina Rönn ◽  
Charlotte Ling ◽  
◽  
Keyword(s):  
Type 2 Diabetes ◽  
Dna Methylation ◽  
Adipose Tissue ◽  
Human Adipose Tissue ◽  
Short Review ◽  
Methylation Pattern ◽  
Cellular Level ◽  
Genetic And Environmental Factors ◽  
The Impact

It is well established that exercise promotes health, and reduces people’s risks for developing type 2 diabetes and becoming obese. But just how exercise performs this, at a cellular level, and what molecular and physiologic steps are involved and in what order, are still not fully understood. Metabolic disorders are often influenced by interactions between genetic and environmental factors. One possible explanation for how the environment may influence the genome is through epigenetic mechanisms–that is–chemical modifications to the DNA itself. Epigenetic factors include, for example, DNA methylation, histone modifications, and different RNA-mediated processes, which all have the ability to bind to DNA or affect the chromatin structure and thereby change how specific genes are interpreted and expressed. In this short review, we focus on describing how exercise influences the genome-wide DNA methylation pattern, including candidate genes for obesity and type 2 diabetes, in human adipose tissue.

The Impact of Arsenic Exposure on Whole Blood DNA Methylation: An Epigenome-Wide Study of Bangladeshi Adults

2018 ◽  
Vol 2018 (1) ◽  
Author(s):  
Kathryn Demanelis ◽  
Maria Argos ◽  
Lin Tong ◽  
Justin Shinkle ◽  
Mekala Sabarinathan ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Whole Blood ◽  
Arsenic Exposure ◽  
Impact Of Arsenic ◽  
The Impact

scholarly journals Sex-specific Relationships Between Il-3, Il-7 and Lipids in African Americans

2020 ◽  
Author(s):  
Ariel Williams ◽  
Catherine Wooten ◽  
Quantil Melendez ◽  
Natasha Greene ◽  
Dayami Lopez ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
African Americans ◽  
Immune Responses ◽  
Sex Chromosome ◽  
Serum Levels ◽  
Serum Samples ◽  
Chronic Disorder ◽  
High Hba1c ◽  
Visceral Adipose ◽  
The Impact

Abstract Purpose: Obesity, a complex chronic disorder characterized by the enlargement of adipose tissue, has a multifactorial etiology. Adipose tissue is now recognized as an active tissue in the regulation of inflammation. Sex chromosome genes and hormones influences immune responses between males and females. Inflammation is rampant in obesity due to the expansion of visceral adipose tissue leading to insulin resistance resulting in type-2 diabetes (T2D). Differences in sex may lead to varied immune responses to T2D.Methods: A total of 116 serum samples were collected from African Americans: 68 women and 48 men. All participants had a BMI > 30. This group consists of 49 normal HbA1c and 71 high HbA1c participants. This study was designed to determine the impact of current circulating glucose on current serum IL-3 and IL-7 levels.Results:Serum cytokine levels are influenced by circulating high glucose and it varies based on sex. We found in women, IL-3 and IL-7 levels were upregulated 1.7-fold in the presence of high circulating glucose. In men, IL-3 levels were downregulated 1.5-fold and IL-7 levels downregulated 1.3-fold in the presence of high circulating glucose. IL-3 and IL-7 serum levels are also correlated with several lipid parameters.Conclusion: IL-3 and IL-7 are members of a complex network of cytokines that play a role in chronic inflammation. Inflammatory signaling impact several diseases including obesity, T2D, atherosclerosis and dyslipidemia. A better understanding of the pathological signaling of cytokines will help facilitate our understanding of inflammation in these diseases.

DNA methylation of the Klf14 gene region in whole blood cells provides prediction for the chronic inflammation in the adipose tissue

2018 ◽  
Vol 497 (3) ◽  
pp. 908-915 ◽  
Author(s):  
Chihiro Iwaya ◽  
Hidetoshi Kitajima ◽  
Ken Yamamoto ◽  
Yasutaka Maeda ◽  
Noriyuki Sonoda ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Adipose Tissue ◽  
Chronic Inflammation ◽  
Whole Blood ◽  
Blood Cells ◽  
Gene Region ◽  
Whole Blood Cells

scholarly journals Adipose Tissue Epigenetic Profile in Obesity-Related Dysglycemia - A Systematic Review

2021 ◽  
Vol 12 ◽  
Author(s):  
Sara Andrade ◽  
Tiago Morais ◽  
Ionel Sandovici ◽  
Alexandre L. Seabra ◽  
Miguel Constância ◽  
...  
Keyword(s):  
Systematic Review ◽  
Dna Methylation ◽  
Adipose Tissue ◽  
Whole Blood ◽  
Intracellular Signaling ◽  
Phenotypic Variability ◽  
Normal Weight ◽  
Small Gtpases ◽  
Metabolic Complications ◽  
Epigenetic Marks

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.

scholarly journals Anti-diabetic effects of a theaflavin-enriched black tea extract in the obese ZDF rat model

2018 ◽  
Vol 3 ◽  
pp. 151-160 ◽  
Author(s):  
Alexander Gosslau ◽  
Emmanuel Zachariah ◽  
Shiming Li ◽  
Chi-Tang Ho
Keyword(s):  
Adipose Tissue ◽  
Weight Gain ◽  
Whole Blood ◽  
Black Tea ◽  
Blood Analysis ◽  
Epididymal Adipose Tissue ◽  
Positive Effects ◽  
Black Tea Extract ◽  
Tea Extract ◽  
The Impact

Effects of a theaflavin-enriched black tea extract (BTE) against type 2 diabetes (T2D) were analyzed using the obese ZDF model. ZDF rats were hyperglycemic, dyslipidemic and express pro-inflammatory markers. BTE was well tolerated and caused an elevation of fasted and fed glucose as well as lower glucose tolerance in contrast to hypoglycemic effects by metformin. However, the BTE group showed decreased levels of LDL and triacylglycerols which corresponded to an increase in free fatty acids. Positive effects against dyslipidemia of BTE corresponded to a significant decrease in weight gain. The impact on inflammatory pathways was analyzed by expression analysis of inflammatory mediators in whole blood and epididymal adipose tissue using TaqMan PCR and ELISA. Whole blood analysis revealed a significant down-regulation of ICAM-1 and TNF-α, whereas IL-4, IL-6, IL-10, IL-13 and IFN-γ were elevated to higher levels as compared to ibuprofen. In adipose tissue, BTE treatment induced an upregulation of COX-2 and IL-6. Thus, BTE treatment showed strong effects against systemic inflammation and caused a reduction of weight gain with positive effects against dyslipidemia. The complexity of signaling pathways leading to complications in diabetes suggest a treatment of BTE in combination with antidiabetic therapeutics as promising strategy against T2D.

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