A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
Macrophage deletion of Noc4l triggers endosomal TLR4/TRIF signal and leads to insulin resistance
Tekijät: Qin Yongli, Jia Lina, Liu Huijiao, Ma Wenqiang, Ren Xinmin, Li Haifeng, Liu Yuanwu, Li Haiwen, Ma Shuoqian, Liu Mei, Li Pingping, Yan Jinghua, Zhang Jiyan, Guo Yangdong, You Hua, Guo Yan, Rahman Nafis A., Wolczynski Slawomir, Kretowski Adam, Li Dangsheng, Li Xiru, Ren Fazheng, Li Xiangdong
Kustantaja: NATURE PORTFOLIO
Julkaisuvuosi: 2021
Journal: Nature Communications
Tietokannassa oleva lehden nimi: NATURE COMMUNICATIONS
Lehden akronyymi: NAT COMMUN
Artikkelin numero: ARTN 6121
Vuosikerta: 12
Numero: 1
Sivujen määrä: 18
eISSN: 2041-1723
DOI: https://doi.org/10.1038/s41467-021-26408-3
Verkko-osoite: https://www.nature.com/articles/s41467-021-26408-3
Rinnakkaistallenteen osoite: https://research.utu.fi/converis/portal/detail/Publication/68064855
In obesity, macrophages drive a low-grade systemic inflammation (LSI) and insulin resistance (IR). The ribosome biosynthesis protein NOC4 (NOC4) mediates 40 S ribosomal subunits synthesis in yeast. Hereby, we reported an unexpected location and function of NOC4L, which was preferentially expressed in human and mouse macrophages. NOC4L was decreased in both obese human and mice. The macrophage-specific deletion of Noc4l in mice displayed IR and LSI. Conversely, Noc4l overexpression by lentivirus treatment and transgenic mouse model improved glucose metabolism in mice. Importantly, we found that Noc4l can interact with TLR4 to inhibit its endocytosis and block the TRIF pathway, thereafter ameliorated LSI and IR in mice.Macrophage inflammation promotes insulin resistance during diet-induced obesity. Here the authors show that macrophage NOC4L is decreased in humans and mice with obesity, that macrophage NOC4L deficiency aggravated high-fat diet induced inflammation and insulin resistance, and that NOC4L interacts with toll-like receptor 4, to inhibit endocytosis, and thus blocks TLF4/TRIF inflammatory signaling.
Ladattava julkaisu This is an electronic reprint of the original article. |  |
