| Autor: |
Yaoyu Zou, Peng Lu, Juan Shi, Wen Liu, Minglan Yang, Shaoqian Zhao, Na Chen, Maopei Chen, Yingkai Sun, Aibo Gao, Qingbo Chen, Zhiguo Zhang, Qinyun Ma, Tinglu Ning, Xiayang Ying, Jiabin Jin, Xiaxing Deng, Baiyong Shen, Yifei Zhang, Bo Yuan, Sophie Kauderer, Simin Liu, Jie Hong, Ruixin Liu, Guang Ning, Weiqing Wang, Weiqiong Gu, Jiqiu Wang |
| Jazyk: |
angličtina |
| Rok vydání: |
2017 |
| Předmět: |
|
| Zdroj: |
EBioMedicine, Vol 24, Iss C, Pp 64-75 (2017) |
| Druh dokumentu: |
article |
| ISSN: |
2352-3964 |
| DOI: |
10.1016/j.ebiom.2017.09.010 |
| Popis: |
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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
|
