Macrophage deletion of Noc4l triggers endosomal TLR4/TRIF signal and leads to insulin resistance
Autor: | Xiru Li, Yan Guo, Yongli Qin, Wenqiang Ma, Slawomir Wolczynski, Fazheng Ren, Haifeng Li, Xiangdong Li, Yang-Dong Guo, Adam Kretowski, Pingping Li, Jiyan Zhang, Haiwen Li, Yuanwu Liu, Shuoqian Ma, Hua You, Nafis A. Rahman, Lina Jia, Ren Xinmin, Huijiao Liu, Mei Liu, Dangsheng Li, Jinghua Yan |
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Rok vydání: | 2021 |
Předmět: |
Male
Genetically modified mouse Cell biology Endosome Science Immunology General Physics and Astronomy Endosomes Endocytosis Article General Biochemistry Genetics and Molecular Biology Mice Insulin resistance Protein biosynthesis medicine Animals Humans Macrophage Mice Knockout Multidisciplinary Chemistry Macrophages General Chemistry medicine.disease Toll-Like Receptor 4 Adaptor Proteins Vesicular Transport Disease Models Animal TRIF TLR4 Female Insulin Resistance Gene Deletion |
Zdroj: | Nature Communications Nature Communications, Vol 12, Iss 1, Pp 1-18 (2021) |
ISSN: | 2041-1723 |
DOI: | 10.1038/s41467-021-26408-3 |
Popis: | 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. |
Databáze: | OpenAIRE |
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