Hypoxia in 3T3-L1 adipocytes suppresses adipdnectin expression via the PERK and IRE1 unfolded protein response
Hypoxia in 3T3-L1 adipocytes suppresses adipdnectin expression via the PERK and IRE1 unfolded protein response
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DOI：
10.1016/j.bbrc.2017.09.020
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发表时间：
2017-11-04
影响因子：
3.1
通讯作者：
Gu, Ning
中科院分区：
文献类型：
--
作者：
Guo, Qian;Jin, Sanli;Gu, Ning
脂联素是由脂肪细胞产生的一种脂肪细胞因子，具有抗炎、抗凋亡的作用，同时也能增强胰岛素敏感性。患有肥胖症或糖尿病的患者或模型动物通常呈现脂联素的减弱表达。此外，肥胖和糖尿病常伴有脂肪组织缺氧，这可能导致内质网（ER）应激以及脂联素表达降低。本研究旨在探讨未折叠蛋白反应（UPR）在低氧诱导脂联素低表达中的作用。3 T3-L1脂肪细胞缺氧显著降低脂联素的表达，并以时间依赖性方式激活PERK和IRE 1信号通路。ATF 6信号通路在低氧处理后的时间过程中无明显变化。此外，一旦PERK和IRE 1信号通路分别被抑制剂GSK 2656157和4 μ 8 C抑制，缺氧诱导的脂联素表达下调被缓解。总之，这些数据表明，缺氧可以抑制脂联素的表达，激活分化的脂肪细胞中的PERK和IRE 1信号通路，这两条通路参与了缺氧诱导的脂联素表达抑制。(C)2017爱思唯尔公司All rights reserved.
Adiponectin, an adipocytokine produced by adipocytes, functions as an anti-inflammatory and antiapoptotic substance, while also enhancing insulin sensitivity. Patients or model animals with obesity or diabetes typically present attenuated expression of adiponectin. Moreover, obesity and diabetes are often accompanied with hypoxia in adipose tissue, which may result in endoplasmic reticulum (ER) stress as well as low expression of adiponectin. The purpose of this study was to investigate the specific role of the unfolded protein response (UPR) involved in the low expression of adiponectin induced by hypoxia. Subjecting 3T3-L1 adipocytes to hypoxia significantly reduced adiponectin expression and activated the PERK and IRE1 signaling pathways in a time-dependent manner. The ATF6 signaling pathway showed no obvious changes with hypoxia treatment under a similar time course. Moreover, the down-regulated expression of adiponectin induced by hypoxia was relieved once the PERK and IRE1 signaling pathways were suppressed by the inhibitors GSK2656157 and 4 mu 8C, respectively. Overall, these data demonstrate that hypoxia can suppress adiponectin expression and activate the PERK and IRE1 signaling pathways in differentiated adipocytes, and this two pathways are involved in the suppression of adiponectin expression induced by hypoxia. (C) 2017 Elsevier Inc. All rights reserved.