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Major vault protein suppresses obesity and atherosclerosis through inhibiting IKK-NF-?B signaling mediated inflammation.


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-?B 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 ?-helical domain inhibits the activity of TRAF6 and suppresses macrophage inflammation. Our results demonstrate that macrophage MVP constitutes a key constraint of NF-?B signaling thereby suppressing metabolic diseases.

SUBMITTER: Ben J 

PROVIDER: S-EPMC6470148 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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

Ben Jingjing J   Jiang Bin B   Wang Dongdong D   Liu Qingling Q   Zhang Yongjing Y   Qi Yu Y   Tong Xing X   Chen Lili L   Liu Xianzhong X   Zhang Yan Y   Zhu Xudong X   Li Xiaoyu X   Zhang Hanwen H   Bai Hui H   Yang Qing Q   Ma Junqing J   Wiemer Erik A C EAC   Xu Yong Y   Chen Qi Q  

Nature communications 20190417 1


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  ...[more]

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