Type I interferon sensing unlocks dormant adipocyte inflammatory potential
Type I interferon sensing unlocks dormant adipocyte inflammatory potential
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DOI：
10.1038/s41467-020-16571-4
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发表时间：
2020-06-02
影响因子：
16.6
通讯作者：
Divanovic, Senad
中科院分区：
文献类型：
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作者：
Chan, Calvin C.;Damen, Michelle S. M. A.;Divanovic, Senad
白色脂肪组织炎症，部分通过骨髓细胞的贡献，是肥胖症发病机制的核心。调节脂肪细胞炎症潜能的机制以及这种炎症在疾病发病机制中的后续影响仍然不清楚。我们表明，激活的I型干扰素（IFN）/IFN α受体（IFNAR）轴放大脂肪细胞的炎症活力和发现休眠基因表达模式类似于炎症髓样细胞。IFN β感应促进脂肪细胞糖酵解，而糖酵解抑制阻碍IFN β驱动的脂肪细胞内炎症。肥胖驱动的I型IFN轴的诱导和脂肪细胞IFNAR信号传导的激活有助于小鼠中肥胖相关的发病机制。值得注意的是，IFN β效应在人类脂肪细胞中是保守的，并且I型IFN/IFNAR轴相关特征的检测与人类中肥胖驱动的代谢紊乱正相关。总的来说，我们的研究结果揭示了I型IFN/IFNAR轴调节髓细胞和脂肪细胞中统一的炎症特征的能力，并暗示了脂肪细胞炎症在疾病发病机制中的未被充分认识的贡献。
White adipose tissue inflammation, in part via myeloid cell contribution, is central to obesity pathogenesis. Mechanisms regulating adipocyte inflammatory potential and consequent impact of such inflammation in disease pathogenesis remain poorly defined. We show that activation of the type I interferon (IFN)/IFN alpha receptor (IFNAR) axis amplifies adipocyte inflammatory vigor and uncovers dormant gene expression patterns resembling inflammatory myeloid cells. IFN beta-sensing promotes adipocyte glycolysis, while glycolysis inhibition impeded IFN beta-driven intra-adipocyte inflammation. Obesity-driven induction of the type I IFN axis and activation of adipocyte IFNAR signaling contributes to obesity-associated pathogenesis in mice. Notably, IFN beta effects are conserved in human adipocytes and detection of the type I IFN/IFNAR axis-associated signatures positively correlates with obesity-driven metabolic derangements in humans. Collectively, our findings reveal a capacity for the type I IFN/IFNAR axis to regulate unifying inflammatory features in both myeloid cells and adipocytes and hint at an underappreciated contribution of adipocyte inflammation in disease pathogenesis.