Altered DNA methylation in liver and adipose tissues derived from individuals with obesity and type 2 diabetes.
Altered DNA methylation in liver and adipose tissues derived from individuals with obesity and type 2 diabetes.
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DOI：
10.1186/s12881-018-0542-8
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发表时间：
2018-02-21
影响因子：
--
通讯作者：
Orozco L
中科院分区：
文献类型：
--
作者：
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
肥胖是公认的胰岛素抵抗和2型糖尿病（T2 D）的危险因素，尽管这种关系的确切机制仍然未知。在这项研究中，我们确定了影响T2 D发病机制的DNA甲基化的改变，在皮下和内脏脂肪组织，肝脏和血液中的肥胖个体。该研究包括患有肥胖症的个体，有和没有T2 D。从这些患者中，我们获得了肝脏组织（n = 16），内脏和皮下脂肪组织（n = 30）和外周血（n = 38）的样本。我们使用Illumina Infinium人类甲基化阵列分析了DNA甲基化，并使用HumanHT-12表达微珠芯片阵列分析了基因表达谱。DNA甲基化谱分析显示，在所有组织中，患有和不患有T2 D的个体之间有几个基因座存在差异甲基化。异常甲基化主要发生在肝脏和内脏脂肪组织。基因本体分析的基因改变DNA甲基化揭示丰富的条款有关的葡萄糖代谢，脂质代谢，细胞周期调控，并响应创伤。在与胰岛素抵抗、脂肪形成、脂肪储存和炎症相关的基因子集中，发现了四种组织中甲基化改变和基因表达之间的负相关性。我们目前的研究结果提供了额外的证据表明，异常DNA甲基化可能是肥胖个体中T2 D发病机制的相关机制。本文的在线版本（10.1186/s12881-018-0542-8）包含补充材料，可供授权用户使用。
Obesity is a well-recognized risk factor for insulin resistance and type 2 diabetes (T2D), although the precise mechanisms underlying the relationship remain unknown. In this study we identified alterations of DNA methylation influencing T2D pathogenesis, in subcutaneous and visceral adipose tissues, liver, and blood from individuals with obesity. The study included individuals with obesity, with and without T2D. From these patients, we obtained samples of liver tissue (n = 16), visceral and subcutaneous adipose tissues (n = 30), and peripheral blood (n = 38). We analyzed DNA methylation using Illumina Infinium Human Methylation arrays, and gene expression profiles using HumanHT-12 Expression BeadChip Arrays. Analysis of DNA methylation profiles revealed several loci with differential methylation between individuals with and without T2D, in all tissues. Aberrant DNA methylation was mainly found in the liver and visceral adipose tissue. Gene ontology analysis of genes with altered DNA methylation revealed enriched terms related to glucose metabolism, lipid metabolism, cell cycle regulation, and response to wounding. An inverse correlation between altered methylation and gene expression in the four tissues was found in a subset of genes, which were related to insulin resistance, adipogenesis, fat storage, and inflammation. Our present findings provide additional evidence that aberrant DNA methylation may be a relevant mechanism involved in T2D pathogenesis among individuals with obesity. The online version of this article (10.1186/s12881-018-0542-8) contains supplementary material, which is available to authorized users.
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控制不同脂肪库中脂肪细胞分化；对病理生理或治疗的影响。
影响因子：
5.2
作者：
Ma X;Lee P;Chisholm DJ;James DE
通讯作者：
James DE
影响因子：
12.3
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Lokk K;Modhukur V;Rajashekar B;Märtens K;Mägi R;Kolde R;Koltšina M;Nilsson TK;Vilo J;Salumets A;Tõnisson N
通讯作者：
Tõnisson N
影响因子：
64.8
作者：
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通讯作者：
Utzschneider, Kristina M.
影响因子：
4.5
作者：
Dayeh T;Volkov P;Salö S;Hall E;Nilsson E;Olsson AH;Kirkpatrick CL;Wollheim CB;Eliasson L;Rönn T;Bacos K;Ling C
通讯作者：
Ling C
影响因子：
64.8
作者：
Roadmap Epigenomics Consortium;Kundaje A;Meuleman W;Ernst J;Bilenky M;Yen A;Heravi-Moussavi A;Kheradpour P;Zhang Z;Wang J;Ziller MJ;Amin V;Whitaker JW;Schultz MD;Ward LD;Sarkar A;Quon G;Sandstrom RS;Eaton ML;Wu YC;Pfenning AR;Wang X;Claussnitzer M;Liu Y;Coarfa C;Harris RA;Shoresh N;Epstein CB;Gjoneska E;Leung D;Xie W;Hawkins RD;Lister R;Hong C;Gascard P;Mungall AJ;Moore R;Chuah E;Tam A;Canfield TK;Hansen RS;Kaul R;Sabo PJ;Bansal MS;Carles A;Dixon JR;Farh KH;Feizi S;Karlic R;Kim AR;Kulkarni A;Li D;Lowdon R;Elliott G;Mercer TR;Neph SJ;Onuchic V;Polak P;Rajagopal N;Ray P;Sallari RC;Siebenthall KT;Sinnott-Armstrong NA;Stevens M;Thurman RE;Wu J;Zhang B;Zhou X;Beaudet AE;Boyer LA;De Jager PL;Farnham PJ;Fisher SJ;Haussler D;Jones SJ;Li W;Marra MA;McManus MT;Sunyaev S;Thomson JA;Tlsty TD;Tsai LH;Wang W;Waterland RA;Zhang MQ;Chadwick LH;Bernstein BE;Costello JF;Ecker JR;Hirst M;Meissner A;Milosavljevic A;Ren B;Stamatoyannopoulos JA;Wang T;Kellis M
通讯作者：
Kellis M