scholarly journals DNA Methylation in Adipose Tissue and Metabolic Syndrome

2020 ◽  
Vol 9 (9) ◽  
pp. 2699
Author(s):  
Sunil K. Panchal ◽  
Lindsay Brown

Epigenetics is the study of heritable phenotype changes that do not involve alterations in the DNA sequence with the processes including DNA methylation, histone modifications and RNA-associated silencing [...]

2019 ◽  
Vol 8 (1) ◽  
pp. 87 ◽  
Author(s):  
Daniel Castellano-Castillo ◽  
Isabel Moreno-Indias ◽  
Lidia Sanchez-Alcoholado ◽  
Bruno Ramos-Molina ◽  
Juan Alcaide-Torres ◽  
...  

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.


2018 ◽  
Vol 64 (1) ◽  
pp. 210-218 ◽  
Author(s):  
Daniel Castellano-Castillo ◽  
Isabel Moreno-Indias ◽  
José Carlos Fernández-García ◽  
Juan Alcaide-Torres ◽  
Inmaculada Moreno-Santos ◽  
...  

Abstract BACKGROUND DNA methylation is one of the epigenetic mechanisms that regulate gene expression. DNA methylation may be modified by environmental and nutritional factors. Thus, epigenetics could potentially provide a mechanism to explain the etiology of metabolic disorders, such as metabolic syndrome (MetS). The aim of this study was to analyze the level of DNA methylation of several lipoprotein lipase (LPL)-promoter-CpG dinucleotides in a CpG island region and relate this to the gene and protein expression levels in human visceral adipose tissue (VAT) from individuals with and without MetS. METHODS VAT samples were collected from laparoscopic surgical patients without and with MetS, and levels of LPL mRNA, LPL protein, and LPL DNA methylation were measured by qPCR, western blot, and pyrosequencing. Biochemical and anthropometric variables were analyzed. Individuals included in a subset underwent a dietary fat challenge test, and levels of postprandial triglycerides were determined. RESULTS We found higher levels of DNA methylation in MetS patients but lower gene expression and protein levels. There was a negative association between LPL methylation and LPL gene expression. We found a positive association between LPL methylation status and abnormalities of the metabolic profile and basal and postprandial triglycerides, whereas LPL gene expression was negatively associated with these abnormalities. CONCLUSIONS We demonstrate that LPL methylation may be influenced by the degree of metabolic disturbances and could be involved in triglyceride metabolism, promoting hypertriglyceridemia and subsequent associated disorders, such as MetS.


2017 ◽  
Author(s):  
Luz D. Orozco ◽  
Colin Farrell ◽  
Christopher Hale ◽  
Liudmilla Rbi ◽  
Arturo Rinaldi ◽  
...  

ABSTRACTMost epigenome-wide association studies to date have been conducted in blood. However, metabolic syndrome is mediated by a dysregulation of adiposity and therefore it is critical to study adipose tissue in order to understand the effects of this syndrome on epigenomes. To determine if natural variation in DNA methylation was associated with metabolic syndrome traits, we profiled global methylation levels in subcutaneous abdominal adipose tissue. We measured association between 32 clinical traits related to diabetes and obesity in 201 people from the Metabolic Syndrome In Men cohort. We performed epigenome-wide association studies between DNA methylation levels and traits, and identified associations for 13 clinical traits in 21 loci. We prioritized candidate genes in these loci using eQTL, and identified 18 high confidence candidate genes, including known and novel genes associated with diabetes and obesity traits. Using methylation deconvolution, we examined which cell types may be mediating the associations, and concluded that most of the loci we identified were specific to adipocytes. We determined whether the abundance of cell types varies with metabolic traits, and found that macrophages increased in abundance with the severity of metabolic syndrome traits. Finally, we developed a DNA methylation based biomarker to assess type II diabetes risk in adipose tissue. In conclusion, our results demonstrate that profiling DNA methylation in adipose tissue is a powerful tool for understanding the molecular effects of metabolic syndrome on adipose tissue, and can be used in conjunction with traditional genetic analyses to further characterize this disorder.


Author(s):  
Ю.И. Шрамко ◽  
А.В. Кубышкин ◽  
А.А. Давыдова ◽  
И.И. Фомочкина ◽  
Л.Л. Алиев ◽  
...  

Цель работы состояла в изучении влияния полифенолов винограда на органы-мишени при экспериментальном метаболическом синдроме у крыс. Методы. В течение 12 недель полифенолы винограда применялись у крыс линии Вистар. Все крысы находились на стандартном рационе. Животные были разделены на 6 групп: 1-я контрольная получала питьевую воду; 2-я контрольная и все 4 экспериментальные - 2,5% раствор фруктозы в качестве питья. 1-я экспериментальная группа дополнительно получала препарат «Фэнокор» с суммарным содержанием полифенолов 181,53 г/дм, 2-я экспериментальная - виноматериал с суммарным содержанием полифенолов 1,73 г/дм; 3-я экспериментальная - виноматериал с суммарным содержанием полифенолов 4,33 г/дм и 4-я экспериментальная - виноматериал с суммарным содержанием полифенолов 8,58 г/дм. После окончания опыта у крыс проводили морфологические исследования висцеральной жировой ткани, тканей миокарда и печени. Результаты. Анализ результатов показал, что применение полифенольных продуктов переработки винограда в концентрациях 181,53 г/дм при моделировании метаболического синдрома приводило к минимизации морфофункциональных нарушений в висцеральной жировой ткани (уменьшение интенсивности лимфоплазмоцитарной инфильтрации), миокарде (мышечные волокна имели типичное строение и адипоциты между ними встречались лишь очагово) и печени (имелись лишь слабые очаговые дистрофические изменения гепатоцитов). Заключение. Результаты работы свидетельствуют о возможности применения виноматериалов с наибольшей концентрацией полифенолов и препарата «Фэнокор» в коррекции и профилактике поражений при метаболическом синдроме. The aim of this work was to study the effect of grape polyphenols on target organs in rats with experimental metabolic syndrome. Methods. Grape polyphenols were used in Wistar rats for 12 weeks. All rats received a standard diet. The animals were divided into 6 groups: group 1, control, received drinking water; group 2, the second control, and four experimental groups received a 2.5% fructose solution for drinking. The first experimental group additionally received a drug, Fenocor, containing polyphenols at 181.53 g/dm; the second experimental group - wine material containing polyphenols at 1,73 g/dm; the third experimental group - wine material containing polyphenols at 4,33 g/dm; and the fourth experimental group - wine material containing polyphenols at 8,58 g/dm. At the end of experiment, morphological studies of visceral adipose tissue, myocardial tissue, and hepatic tissue were performed. Results. The treatment of rats with experimental metabolic syndrome with grape polyphenolic products at a concentration of 181.53 g/dm minimized morphological and functional disorders in visceral adipose tissue (intensity of lymphoplasmocytic infiltration was decreased), myocardium (muscle fibers had normal structure with only occasional adipocytes between them), and liver (only slight focal degenerative changes were observed in hepatocytes). Conclusion. The study indicated a possibility of using wine materials with the highest concentration of polyphenols and the drug Fenocor for correction and prevention of damages in metabolic syndrome.


Author(s):  
Irfete S. Fetahu ◽  
Sabine Taschner-Mandl

AbstractNeuroblastoma (NB) is a pediatric cancer of the sympathetic nervous system and one of the most common solid tumors in infancy. Amplification of MYCN, copy number alterations, numerical and segmental chromosomal aberrations, mutations, and rearrangements on a handful of genes, such as ALK, ATRX, TP53, RAS/MAPK pathway genes, and TERT, are attributed as underlying causes that give rise to NB. However, the heterogeneous nature of the disease—along with the relative paucity of recurrent somatic mutations—reinforces the need to understand the interplay of genetic factors and epigenetic alterations in the context of NB. Epigenetic mechanisms tightly control gene expression, embryogenesis, imprinting, chromosomal stability, and tumorigenesis, thereby playing a pivotal role in physio- and pathological settings. The main epigenetic alterations include aberrant DNA methylation, disrupted patterns of posttranslational histone modifications, alterations in chromatin composition and/or architecture, and aberrant expression of non-coding RNAs. DNA methylation and demethylation are mediated by DNA methyltransferases (DNMTs) and ten-eleven translocation (TET) proteins, respectively, while histone modifications are coordinated by histone acetyltransferases and deacetylases (HATs, HDACs), and histone methyltransferases and demethylases (HMTs, HDMs). This article focuses predominately on the crosstalk between the epigenome and NB, and the implications it has on disease diagnosis and treatment.


2021 ◽  
Vol 22 (13) ◽  
pp. 6783
Author(s):  
Renata Orłowska ◽  
Katarzyna A. Pachota ◽  
Wioletta M. Dynkowska ◽  
Agnieszka Niedziela ◽  
Piotr T. Bednarek

A plant genome usually encompasses different families of transposable elements (TEs) that may constitute up to 85% of nuclear DNA. Under stressful conditions, some of them may activate, leading to sequence variation. In vitro plant regeneration may induce either phenotypic or genetic and epigenetic changes. While DNA methylation alternations might be related, i.e., to the Yang cycle problems, DNA pattern changes, especially DNA demethylation, may activate TEs that could result in point mutations in DNA sequence changes. Thus, TEs have the highest input into sequence variation (SV). A set of barley regenerants were derived via in vitro anther culture. High Performance Liquid Chromatography (RP-HPLC), used to study the global DNA methylation of donor plants and their regenerants, showed that the level of DNA methylation increased in regenerants by 1.45% compared to the donors. The Methyl-Sensitive Transposon Display (MSTD) based on methylation-sensitive Amplified Fragment Length Polymorphism (metAFLP) approach demonstrated that, depending on the selected elements belonging to the TEs family analyzed, varying levels of sequence variation were evaluated. DNA sequence contexts may have a different impact on SV generated by distinct mobile elements belonged to various TE families. Based on the presented study, some of the selected mobile elements contribute differently to TE-related SV. The surrounding context of the TEs DNA sequence is possibly important here, and the study explained some part of SV related to those contexts.


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