| 论文编号: |
|
| 第一作者所在部门: |
|
| 中文论文题目: |
Generation of a genetically modified pig model with CREBRF R457Q variant |
| 英文论文题目: |
Generation of a genetically modified pig model with CREBRF R457Q variant |
| 作者: |
Yingying Li,Hai Wang,Huangyao Chen,Yuan Liao,Shixue Gou,Quanmei Yan,Zhenpeng Zhuang,Hao Li,Jiaowei Wang,Yangyang Suo,Ting Lan,Yang Liu,Yu Zhao,Qingjian Zou,Tao Nie,Xiaoyan Hui,Liangxue Lai,Donghai Wu,Nana Fan |
| 论文出处: |
|
| 刊物名称: |
FASEB Journal |
| 年: |
2022 |
| 卷: |
36 |
| 期: |
11 |
| 页: |
e22611 |
| 联系作者: |
Liangxue Lai |
| 收录类别: |
|
| 影响因子: |
5.834 |
| 摘要: |
Obesity is among the strongest risk factors for type 2 diabetes (T2D). The CREBRF missense allele rs373863828 (p. Arg457Gln, p. R457Q) is associated with increased body mass index but reduced risk of T2D in people of Pacific ancestry. To investigate the functional consequences of the CREBRF variant, we introduced the corresponding human mutation R457Q into the porcine genome. The CREBRFR457Q pigs displayed dramatically increased fat deposition, which was mainly distributed in subcutaneous adipose tissue other than visceral adipose tissue. The CREBRFR457Q variant promoted preadipocyte differentiation. The increased differentiation capacity of precursor adipocytes conferred pigs the unique histological phenotype that adipocytes had a smaller size but a greater number in subcutaneous adipose tissue (SAT) of CREBRFR457Q variant pigs. In addition, in SAT of CREBRFR457Q pigs, the contents of the peroxidative metabolites 4-hydroxy-nonenal and malondialdehyde were significantly decreased, while the activity of antioxidant enzymes, such as glutathione peroxidase, superoxide dismutase, and catalase, was increased, which was in accordance with the declined level of the reactive oxygen species (ROS) in CREBRFR457Q pigs. Together, these data supported a causal role of the CREBRFR457Q variant in the pathogenesis of obesity, partly via adipocyte hyperplasia, and further suggested that reduced oxidative stress in adipose tissue may mediate the relative metabolic protection afforded by this variant despite the related obesity. |
| 英文摘要: |
|
| 外单位作者单位: |
|
| 备注: |
|
