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IRX3 Promotes the Browning ofWhite Adipocytes and Its Rare Variants are Associated with Human Obesity Risk 期刊论文

编号：

f7729f7c-ae87-4d05-b5fa-b9528fd8d5ce
作者：

Zou, Yaoyu^[1,2,3] Lu, Peng^[1] Shi, Juan^[2] Liu, Wen^[2] Yang, Minglan^[2] Zhao, Shaoqian^[2] Chen, Na^[2] Chen, Maopei^[2] Sun, Yingkai^[2] Gao, Aibo^[2] Chen, Qingbo^[2] Zhang, Zhiguo^[2] Ma, Qinyun^[2] Ning, Tinglu^[1] Ying, Xiayang^[4] Jin, Jiabin^[4] Deng, Xiaxing^[4] Shen, Baiyong^[4] Zhang, Yifei^[2] Yuan, Bo^[5] Kauderer, Sophie^[6,7] Liu, Simin^[6,7] Hong, Jie^[2] Liu, Ruixin^[2] Ning, Guang^[1,2] Wang, Weiqing^[2] Gu, Weiqiong^[2] Wang, Jiqiu^[2]
语种：

English
期刊：

EBIOMEDICINE ISSN：2352-3964 2017 年 24 卷 (64 - 75) ; OCT
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关键词：

IRX3 Beige adipocytes Browning program Genetic variants Obesity
摘要：

Background: IRX3 was recently reported as the effector of the FTO variants. We aimed to test IRX3' s roles in the browning program and to evaluate the association between the genetic variants in IRX3 and human obesity. Methods: IRX3 expression was examined in beige adipocytes in human and mouse models, and further validated in induced beige adipocytes. The browning capacity of primary preadipocytes was assessed with IRX3 knockdown. Luciferase reporter analysis and ChIP assay were applied to investigate IRX3' s effects on UCP1 transcriptional activity. Moreover, genetic analysis of IRX3 was performed in 861 young obese subjects and 916 controls. Results: IRX3 expression was induced in the browning process and was positively correlated with the browning markers. IRX3 knockdown remarkably inhibited UCP1 expression in induced mouse and human beige adipocytes, and also repressed the uncoupled oxygen consumption rate. Further, IRX3 directly bound to UCP1 promoter and increased its transcriptional activity. Moreover, 17 rare heterozygous missense/frameshift IRX3 variants were identified, with a significant enrichment in obese subjects (P = 0.038, OR= 2.27; 95% CI, 1.02-5.05). Conclusions: IRX3 deficiency repressed the browning program of white adipocytes partially by regulating UCP1 transcriptional activity. Rare variants of IRX3 were associated with human obesity. (C) 2017 The Authors. Published by Elsevier B. V. This is an open access article under the CC BY license
推荐引用方式
GB/T 7714：

Zou Yaoyu,Lu Peng,Shi Juan, et al. IRX3 Promotes the Browning ofWhite Adipocytes and Its Rare Variants are Associated with Human Obesity Risk [J].EBIOMEDICINE,2017,24:64-75.
APA：

Zou Yaoyu,Lu Peng,Shi Juan,Liu Wen,&Wang Jiqiu.(2017).IRX3 Promotes the Browning ofWhite Adipocytes and Its Rare Variants are Associated with Human Obesity Risk .EBIOMEDICINE,24:64-75.
MLA：

Zou Yaoyu, et al. "IRX3 Promotes the Browning ofWhite Adipocytes and Its Rare Variants are Associated with Human Obesity Risk" .EBIOMEDICINE 24(2017):64-75.

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