LIGHT/TNFSF14 signaling attenuates beige fat biogenesis
LIGHT/TNFSF14 signaling attenuates beige fat biogenesis
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LIGHT/TNFSF14 信号减弱米色脂肪生物发生
DOI：
10.1096/fj.201800792r
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发表时间：
2019-02-01
期刊：
影响因子：
4.8
通讯作者：
Wang, Yugang
中科院分区：
文献类型：
--
作者：
Kou, Yanbo;Liu, Qingya;Wang, Yugang
调节米色脂肪生成的生理信号仍不完全清楚，特别是那些限制褐变和防止能量过度消耗的信号。在这项研究中，TNF家族成员细胞因子淋巴毒素样诱导蛋白与糖蛋白D竞争疱疹病毒进入T细胞（LIGHT），也称为TNF超家族蛋白14（TNFSF14），可以抑制脂肪前体分化为米色脂肪细胞。在急性冷应激下，小鼠的光缺乏加速了皮下白色脂肪组织（scWAT）的褐变。进一步的实验表明，LIGHT 与脂肪前体上的淋巴毒素受体 (LTR) 相互作用，阻断了米色脂肪的生物合成。 LTR 信号减弱了 JNK 通路，这有助于其抗米色效应。使用小分子抑制剂阻断 JNK 激活可防止寒冷诱导的 scWAT 米色。此外，LIGHT/LTR 信号充当白色脂肪生成的衰减器。在高脂肪饮食喂养过程中，光照不足会促进小鼠肥胖。这些发现将光轴确定为脂肪组织稳态的调节器，并表明 LIGHT 信号传导是一种转移能量以支持免疫激活的机制。Kou, Y.、Liu, Q.、Liu, W.、Sun, H.、Liang, M.、Kong, F.、Zhang, B.、Wei, Y.、Liu, Z.、Wang, Y. LIGHT/TNFSF14 信号传导减弱米色脂肪生物发生。
The physiologic signals that regulate beige adipogenesis remain incompletely understood, especially those that limit browning and prevent overexpenditure of energy. In this study, the TNF family member cytokine lymphotoxin-like inducible protein that competes with glycoprotein D for herpesvirus entry on T cells (LIGHT), also known as TNF super family protein 14 (TNFSF14), can inhibit adipose precursor differentiation into beige adipocytes. In acute cold stress, LIGHT deficiency in mice accelerated browning in the subcutaneous white adipose tissue (scWAT). Further experiments showed that LIGHT interacting with lymphotoxin- receptor (LTR) on adipose precursors blocked beige fat biogenesis. LTR signals attenuated the JNK pathway, which contributed to their antibeiging effect. Blocking JNK activation using a small molecular inhibitor prevented cold-induced scWAT beiging. Furthermore, LIGHT/LTR signals acted as an attenuator of white adipogenesis. LIGHT deficiency in mice promoted obesity during high-fat diet feeding. These findings identify the LIGHT axis as a regulator of adipose tissue homeostasis and suggest that LIGHT signaling functions as a mechanism to divert energy in favor of immune activation.Kou, Y., Liu, Q., Liu, W., Sun, H., Liang, M., Kong, F., Zhang, B., Wei, Y., Liu, Z., Wang, Y. LIGHT/TNFSF14 signaling attenuates beige fat biogenesis.