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Major vault protein suppresses obesity and atherosclerosis through inhibiting IKK–NF-κB signaling mediated inflammation

Author

Listed:
  • Jingjing Ben

    (Nanjing Medical University)

  • Bin Jiang

    (Nanjing Medical University)

  • Dongdong Wang

    (Nanjing Medical University)

  • Qingling Liu

    (Nanjing Medical University)

  • Yongjing Zhang

    (Nanjing Medical University)

  • Yu Qi

    (Nanjing Medical University)

  • Xing Tong

    (Nanjing Medical University)

  • Lili Chen

    (Nanjing Medical University)

  • Xianzhong Liu

    (Nanjing Medical University)

  • Yan Zhang

    (Nanjing Medical University)

  • Xudong Zhu

    (Nanjing Medical University)

  • Xiaoyu Li

    (Nanjing Medical University)

  • Hanwen Zhang

    (Nanjing Medical University)

  • Hui Bai

    (Nanjing Medical University)

  • Qing Yang

    (Nanjing Medical University)

  • Junqing Ma

    (Nanjing Medical University)

  • Erik A. C. Wiemer

    (Erasmus University Medical Center)

  • Yong Xu

    (Nanjing Medical University)

  • Qi Chen

    (Nanjing Medical University)

Abstract

Macrophage-orchestrated, low-grade chronic inflammation plays a pivotal role in obesity and atherogenesis. However, the underlying regulatory mechanisms remain incompletely understood. Here, we identify major vault protein (MVP), the main component of unique cellular ribonucleoprotein particles, as a suppressor for NF-κB signaling in macrophages. Both global and myeloid-specific MVP gene knockout aggravates high-fat diet induced obesity, insulin resistance, hepatic steatosis and atherosclerosis in mice. The exacerbated metabolic disorders caused by MVP deficiency are accompanied with increased macrophage infiltration and heightened inflammatory responses in the microenvironments. In vitro studies reveal that MVP interacts with TRAF6 preventing its recruitment to IRAK1 and subsequent oligomerization and ubiquitination. Overexpression of MVP and its α-helical domain inhibits the activity of TRAF6 and suppresses macrophage inflammation. Our results demonstrate that macrophage MVP constitutes a key constraint of NF-κB signaling thereby suppressing metabolic diseases.

Suggested Citation

  • Jingjing Ben & Bin Jiang & Dongdong Wang & Qingling Liu & Yongjing Zhang & Yu Qi & Xing Tong & Lili Chen & Xianzhong Liu & Yan Zhang & Xudong Zhu & Xiaoyu Li & Hanwen Zhang & Hui Bai & Qing Yang & Jun, 2019. "Major vault protein suppresses obesity and atherosclerosis through inhibiting IKK–NF-κB signaling mediated inflammation," Nature Communications, Nature, vol. 10(1), pages 1-15, December.
  • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-09588-x
    DOI: 10.1038/s41467-019-09588-x
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