Obesity-induced endoplasmic reticulum stress suppresses nuclear factor-Y expression
Obesity-induced endoplasmic reticulum stress suppresses nuclear factor-Y expression
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肥胖诱导的内质网应激抑制核因子-Y 表达
DOI：
10.1007/s11010-016-2879-7
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发表时间：
2017-02-01
影响因子：
4.3
通讯作者：
Su, Zhiguang
中科院分区：
文献类型：
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作者：
Liu, Yulan;Zhang, Yuwei;Su, Zhiguang
核转录因子Y （NF-Y）是一种进化保守的转录因子，由NF-YA、NF-YB和NF-YC三个亚基组成。NF-Y在脂肪前细胞维持和/或脂肪形成中起着至关重要的作用。脂肪细胞NF-YA功能障碍导致与代谢并发症相关的脂肪组织的年龄依赖性进行性损失。内质网应激在肥胖发病机制中起着重要的调节作用。然而，目前尚不清楚NF-YA是否参与内质网应激介导的肥胖发病机制。我们首先研究了内质网应激对培养的3T3-L1脂肪细胞中NF-YA表达的影响；然后在ob/ob遗传性肥胖小鼠中，我们测试了减轻内质网应激的化学伴侣对NF-YA表达水平的影响。随后，我们在3T3-L1细胞中使用放线菌素D抑制新的mRNA合成，以探索调节NF-YA表达的机制。最后，我们评估了PPARg参与内质网应激对NF-YA表达的调节。我们证明肥胖和化学伴侣诱导的内质网应激均抑制NF-YA表达，化学伴侣减轻内质网应激可恢复ob/ob小鼠NF-YA表达。此外，我们发现内质网应激通过参与过氧化物酶体增殖物激活受体γ (ppar)抑制NF-YA mRNA转录。激活PPARg可改善内质网应激诱导的NF-YA抑制。我们的研究结果可能指出NF-YA在慢性肥胖的应激条件下的可能作用，内质网应激可能通过NF-YA耗竭参与肥胖的发病机制。
Nuclear transcription factor Y (NF-Y) is an evolutionarily conserved transcription factor composed of three subunits, NF-YA, NF-YB, and NF-YC. NF-Y plays crucial roles in pre-adipocyte maintenance and/or commitment to adipogenesis. NF-YA dysfunction in adipocyte resulted in an age-dependent progressive loss of adipose tissue associated with metabolic complications. Endoplasmic reticulum (ER) stress has emerged as an important mediator in the pathogenesis of obesity. However, it is not known if NF-YA is involved in the ER stress-mediated pathogenesis of obesity. We first examined the effects of ER stress on the NF-YA expression in cultured 3T3-L1 adipocytes; then in ob/ob genetic obesity mice, we tested the effect of chemical chaperones alleviating ER stress on the expression levels of NF-YA. Subsequently, we inhibited the new mRNA synthesis using actinomycin D in 3T3-L1 cells to explore the mechanism modulating NF-YA expression. Finally, we evaluated the involvement of PPARg in the regulation of NF-YA expression by ER stress. We demonstrated that both obesity- and chemical chaperone -induced ER stress suppressed NF-YA expression and alleviation of ER stress by chemical chaperone could recover NF-YA expression in ob/ob mice. Moreover, we showed that ER stress suppressed NF-YA mRNA transcription through the involvement of peroxisome proliferator-activated receptor gamma (PPARg). Activation of PPARg ameliorates the ER stress-induced NF-YA suppression. Our findings may point to a possible role of NF-YA in stress conditions that occur in chronic obesity, ER stress might be involved in the pathogenesis of obesity through NF-YA depletion.