Macrophage deletion of Noc4l triggers endosomal TLR4/TRIF signal and leads to insulin resistance

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 i...

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Detalles Bibliográficos
Autores principales: 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., Wołczyński, Sławomir, Kretowski, Adam, Li, Dangsheng, Li, Xiru, Ren, Fazheng, Li, Xiangdong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8531303/
https://www.ncbi.nlm.nih.gov/pubmed/34675215
http://dx.doi.org/10.1038/s41467-021-26408-3
Descripción
Sumario: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.

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