Adipose Tissue Epigenetic Profile in Obesity-Related Dysglycemia - A Systematic Review.
Adipose Tissue Epigenetic Profile in Obesity-Related Dysglycemia - A Systematic Review.
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DOI：
10.3389/fendo.2021.681649
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发表时间：
2021
影响因子：
5.2
通讯作者：
Monteiro MP
中科院分区：
文献类型：
--
作者：
Andrade S;Morais T;Sandovici I;Seabra AL;Constância M;Monteiro MP
肥胖是血糖异常的主要危险因素，包括2型糖尿病（T2D）。然而，代谢谱存在广泛的表型差异。组织特异性表观遗传修饰可以部分解释观察到的表型变异性。本系统综述的目的是总结人类脂肪组织（AT）中表征超重或肥胖相关胰岛素抵抗（IR）和血糖异常状态的表观遗传特征的现有数据，并通过使用无偏倚的生物信息学方法确定潜在的潜在机制。过去十年发表的关于代谢不健康超重/肥胖（MUHO）个体与正常体重个体或代谢健康超重/肥胖（MHO）个体在人类AT中表观遗传标记比较的原始数据进行了评估。此外，这些表观遗传标记与IR/血糖异常特征（包括T2D）的关联被编译。与MHO个体相比，我们在MUHO个体的AT中编目了超过2000个差异甲基化区域（DMRs；高于5%的临界值）。这些DNA甲基化变化不太可能发生在启动子区域周围，并且在涉及细胞内信号传导（由小gtpase， ERK1/2信号传导和细胞内运输介导的信号转导）的位点上富集。我们还发现了一个由7个转录因子组成的网络，这些转录因子可能在靶向MUHO受试者AT中特定基因的DNA甲基化变化中发挥重要作用，从而促进肥胖相关IR/T2D的发病。此外，我们在at和全血中发现8个基因的CpG位点存在差异甲基化，这表明全血中的DMRs可能被用作MUHO的生物标志物。将关键组织（如AT）的表观遗传改变与人类肥胖的代谢并发症联系起来的总体证据仍然非常有限，这突出了进一步研究的必要性，特别是那些关注DNA甲基化以外的表观遗传标记的研究。我们的初步分析表明，DNA甲基化模式可以潜在地区分MUHO和MHO，并为为什么一些肥胖者不易患血糖异常提供了新的线索。确定at特异性的表观遗传靶点也可能导致新的方法来改变肥胖个体向代谢性疾病的进展。，标识符CRD42021227237。
Obesity 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. The 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. Original 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. We 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. The 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. , identifier CRD42021227237.
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影响因子：
29
作者：
Barres, Romain;Yan, Jie;Zierath, Juleen R.
通讯作者：
Zierath, Juleen R.
影响因子：
3.5
作者：
Albao, Dominic S.;Cutiongco-de la Paz, Eva Maria;Seielstad, Mark
通讯作者：
Seielstad, Mark
影响因子：
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Barajas-Olmos F;Centeno-Cruz F;Zerrweck C;Imaz-Rosshandler I;Martínez-Hernández A;Cordova EJ;Rangel-Escareño C;Gálvez F;Castillo A;Maydón H;Campos F;Maldonado-Pintado DG;Orozco L
通讯作者：
Orozco L
影响因子：
29
作者：
Barres, Romain;Osler, Megan E.;Zierath, Juleen R.
通讯作者：
Zierath, Juleen R.
影响因子：
7
作者：
Cassandri M;Smirnov A;Novelli F;Pitolli C;Agostini M;Malewicz M;Melino G;Raschellà G
通讯作者：
Raschellà G