Adipose tissue gene expression and metabolic health of obese adults.
Adipose tissue gene expression and metabolic health of obese adults.
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DOI：
10.1038/ijo.2014.210
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发表时间：
2015-05
影响因子：
4.9
通讯作者：
Sharma, N. K.
中科院分区：
文献类型：
--
作者：
Das, S. K.;Ma, L.;Sharma, N. K.
体重指数（BMI）相似的肥胖受试者在血糖和心脏代谢健康表型方面表现出显著的异质性。然而，定义肥胖个体中代谢特征异质性的基础基因以及确定代谢健康和不健康的表型仍然具有挑战性。我们对30名年龄≥40岁的肥胖男性和女性的皮下脂肪组织转录本进行了无监督的分层聚类分析。尽管所有受试者的BMI相似，但我们发现了两个不同的亚组，一个代谢健康（第1组）和一个代谢不健康（第2组）。与组1相比，组2中的受试者显示出显著更高的总胆固醇（p=0.005）、LDL胆固醇（p=0.006）、OGTT期间的2 h-胰岛素（p=0.015）和更低的胰岛素敏感性（SI，p=0.029）。在第2组受试者中，我们确定了141个基因（例如MMP 9和SPP 1）的显著上调和17个基因（例如NDRG 4和GINS 3）的下调。有趣的是，这些差异表达的转录本富含参与心血管疾病相关过程的基因（p=2.81×10−11-3.74×10−02）和参与免疫和炎症反应的途径（p=8.32×10−5-0.04）。在已发表的GWASs和斑马鱼基因敲除模型中，两个下调基因NDRG 4和GINS 3位于与心脏复极相关的基因组间隔中。我们的研究提供的证据表明，在脂肪组织基因表达网络的扰动是重要的，在定义肥胖受试者的代谢健康。
Obese subjects with a similar body mass index (BMI) exhibit substantial heterogeneity in gluco- and cardio-metabolic heath phenotypes. However, defining genes that underlie the heterogeneity of metabolic features among obese individuals and determining metabolically healthy and unhealthy phenotypes remain challenging. We conducted unsupervised hierarchical clustering analysis of subcutaneous adipose tissue transcripts from 30 obese men and women ≥40 years old. Despite similar BMIs in all subjects, we found two distinct subgroups, one metabolically healthy (Group 1) and one metabolically unhealthy (Group 2). Subjects in Group 2 showed significantly higher total cholesterol (p=0.005), LDL cholesterol (p=0.006), 2h-Insulin during OGTT (p=0.015) and lower insulin sensitivity (SI, p=0.029) compared to Group 1. We identified significant up-regulation of 141 genes (e.g. MMP9 and SPP1) and down-regulation of 17 genes (e.g. NDRG4 and GINS3) in group 2 subjects. Intriguingly, these differentially expressed transcripts were enriched for genes involved in cardiovascular disease-related processes (p=2.81×10−11–3.74×10−02) and pathways involved in immune and inflammatory response (p=8.32×10−5–0.04). Two down-regulated genes, NDRG4 and GINS3, have been located in a genomic interval associated with cardiac repolarization in published GWASs and zebra fish knockout models. Our study provides evidence that perturbations in the adipose tissue gene expression network are important in defining metabolic health in obese subjects.
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DOI：
10.1073/pnas.091062498
发表时间：
2001-04-24
影响因子：
11.1
作者：
Tusher, VG;Tibshirani, R;Chu, G
通讯作者：
Chu, G
影响因子：
7.7
作者：
Qatanani M;Tan Y;Dobrin R;Greenawalt DM;Hu G;Zhao W;Olefsky JM;Sears DD;Kaplan LM;Kemp DM
通讯作者：
Kemp DM
影响因子：
30.8
作者：
Pfeufer, Arne;Sanna, Serena;Arking, Dan E.;Mueller, Martina;Gateva, Vesela;Fuchsberger, Christian;Ehret, Georg B.;Orru, Marco;Pattaro, Cristian;Koettgen, Anna;Perz, Siegfried;Usala, Gianluca;Barbalic, Maja;Li, Man;Puetz, Benno;Scuteri, Angelo;Prineas, Ronald J.;Sinner, Moritz F.;Gieger, Christian;Najjar, Samer S.;Kao, W. H. Linda;Muehleisen, Thomas W.;Dei, Mariano;Happle, Christine;Moehlenkamp, Stefan;Crisponi, Laura;Erbel, Raimund;Joeckel, Karl-Heinz;Naitza, Silvia;Steinbeck, Gerhard;Marroni, Fabio;Hicks, Andrew A.;Lakatta, Edward;Mueller-Myhsok, Bertram;Pramstaller, Peter P.;Wichmann, H-Erich;Schlessinger, David;Boerwinkle, Eric;Meitinger, Thomas;Uda, Manuela;Coresh, Josef;Kaeaeb, Stefan;Abecasis, Goncalo R.;Chakravarti, Aravinda
通讯作者：
Chakravarti, Aravinda
影响因子：
5.8
作者：
Das, Swapan K.;Sharma, Neeraj K.;Elbein, Steven C.
通讯作者：
Elbein, Steven C.
影响因子：
64.8
作者：
Van Gaal, Luc F.;Mertens, Ilse L.;De Block, Christophe E.
通讯作者：
De Block, Christophe E.