| First Author | Ben J | Year | 2019 |
| Journal | Nat Commun | Volume | 10 |
| Issue | 1 | Pages | 1801 |
| PubMed ID | 30996248 | Mgi Jnum | J:275578 |
| Mgi Id | MGI:6305674 | Doi | 10.1038/s41467-019-09588-x |
| Citation | Ben J, et al. (2019) Major vault protein suppresses obesity and atherosclerosis through inhibiting IKK-NF-kappaB signaling mediated inflammation. Nat Commun 10(1):1801 |
| abstractText | 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-kappaB 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 alpha-helical domain inhibits the activity of TRAF6 and suppresses macrophage inflammation. Our results demonstrate that macrophage MVP constitutes a key constraint of NF-kappaB signaling thereby suppressing metabolic diseases. |
