The differential role of Hif1β/Arnt and the hypoxic response in adipose function, fibrosis, and inflammation.
The differential role of Hif1β/Arnt and the hypoxic response in adipose function, fibrosis, and inflammation.
复制标题
DOI：
10.1016/j.cmet.2011.08.006
复制
发表时间：
2011-10-05
期刊：
影响因子：
29
通讯作者：
Kahn CR
中科院分区：
文献类型：
--
作者：
Lee KY;Gesta S;Boucher J;Wang XL;Kahn CR
在肥胖症中，远离脉管系统的脂肪细胞变得缺氧和功能障碍。这种缺氧反应是由缺氧诱导因子（Hif 1 α、Hif 2 α和Hif 3 α）及其专性伴侣Hif 1 β（Arnt）介导的。我们发现，脂肪中缺乏HIF 1 β的小鼠（FH 1 βKO）是瘦的，表现出减少的脂肪细胞大小，并保护免受年龄和饮食诱导的葡萄糖耐受不良。FH 1 βKO脂肪中的VEGF和血管通透性也降低，但饮食诱导的炎症和纤维化没有改变。FH 1 βKO小鼠的脂肪细胞由于Glut 1和Glut 4减少而葡萄糖摄取减少，这反映在Hif 1 β敲低的3 T3-L1脂肪细胞中。Hif 1 β敲低细胞也不能适当地响应缺氧，细胞呼吸减少，线粒体基因表达减少。这些效应中的一部分（但不是全部）通过Hif 1 α敲低得以再现。因此，Hif 1 β/Arnt调节葡萄糖摄取、线粒体基因表达和血管通透性以控制脂肪质量和功能，为肥胖治疗提供了新的靶点。
In obesity, adipocytes distant from vasculature become hypoxic and dysfunctional. This hypoxic response is mediated by hypoxia inducible factors (Hif1α, Hif2α, and Hif3α), and their obligate partner Hif1β (Arnt). We show that mice lacking Hif1β in fat (FH1βKO) are lean, exhibit reduced adipocyte size, and are protected from age and diet-induced glucose intolerance. There is also reduced Vegf and vascular permeability in FH1βKO fat, but diet-induced inflammation and fibrosis is unchanged. Adipocytes from FH1βKO mice have reduced glucose uptake due to decreased Glut1 and Glut4, which is mirrored in 3T3-L1 adipocytes with Hif1β knockdown. Hif1β knockdown cells also fail to respond appropriately to hypoxia with reduced cellular respiration and reduced mitochondrial gene expression. Some, but not all, of these effects are reproduced by Hif1α knockdown. Thus, Hif1β/Arnt regulates glucose uptake, mitochondrial gene expression, and vascular permeability to control adipose mass and function, providing a novel target for obesity therapy.
登录
查看更多内容
影响因子：
6
作者：
Heilig, C;Brosius, F;Conner, D
通讯作者：
Conner, D
影响因子：
7.8
作者：
Katic, Masa;Kennedy, Adam R.;Kahn, C. Ronald
通讯作者：
Kahn, C. Ronald
影响因子：
4.8
作者：
Blüher, M;Patti, ME;Kahn, CR
通讯作者：
Kahn, CR
影响因子：
82.9
作者：
Compernolle, V;Brusselmans, K;Carmeliet, P
通讯作者：
Carmeliet, P
影响因子：
64.8
作者：
Maltepe, E;Schmidt, JV;Simon, MC
通讯作者：
Simon, MC