Ifi27 is indispensable for mitochondrial function and browning in adipocytes
Ifi27 is indispensable for mitochondrial function and browning in adipocytes
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Ifi27 对于线粒体功能和脂肪细胞褐变是不可或缺的
DOI：
10.1016/j.bbrc.2018.04.234
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发表时间：
2018-06-18
影响因子：
3.1
通讯作者：
Pan, Dongning
中科院分区：
文献类型：
--
作者：
Jin, Weiwei;Jin, Wenfang;Pan, Dongning
棕色脂肪组织（BAT）是专门用于能量消耗，但调节BAT代谢和活动的信号转导途径还不完全清楚。干扰素（IFN）信号传导是抵抗病毒感染的复杂防御机制。干扰素和干扰素刺激基因（ISGs）对脂肪细胞产生深远的影响。IFN-α诱导蛋白27（IFi 27/ISG 12 a）是一个富含BAT的基因，但关于其在BAT中的作用还未见报道。在这里，我们表明，Ifi 27蛋白定位于线粒体和Ifi 27的表达可以诱导β 3-肾上腺素能激活脂肪组织。敲低Ifi 27导致棕色和米色脂肪细胞中三羧酸循环（TCA）关键酶、电子传递链（ETC）亚基和解偶联蛋白1（Ucp 1）表达减少。而且，由β 3-肾上腺素能激动剂诱导的皮下白色脂肪的布朗宁也被显著阻断。Ifi 27在棕色脂肪细胞中的异位表达具有相反的作用。总之，这些数据表明Ifi 27调节脂肪细胞中的线粒体功能和布朗宁。(C)2018爱思唯尔公司All rights reserved.
Brown adipose tissue (BAT) is specialized for energy expenditure, but the signaling pathways that regulate BAT metabolism and activity are incompletely understood. Interferon (IFN) signaling is a sophisticated defense mechanism to counteract viral infection. IFNs and interferon-stimulated genes (ISGs) are reported to exert profound effects on adipocytes. IFN-alpha inducible protein 27 (Ifi27/ISG12a) is a BAT-enriched gene, yet no any studies on its roles in BAT have been reported. Here, we show that Ifi27 protein localizes to mitochondria and the expression of Ifi27 can be induced by beta 3-adrenergic activation in adipose tissues. Knockdown of Ifi27 leads to reduced expression of key enzymes of tricarboxylic acid cycle (TCA), the subunits of electron transport chain (ETC) and uncoupling protein 1 (Ucp1) in brown and beige adipocytes. Moreover, the browning of subcutaneous white fat induced by beta 3-adrenergic agonist is also dramatically blocked. Ectopic expression of Ifi27 in brown adipocytes has the opposite effects. Together, these data indicate that Ifi27 regulates mitochondrial function and browning in adipocytes. (C) 2018 Elsevier Inc. All rights reserved.