Journal
NATURE COMMUNICATIONS
Volume 12, Issue 1, Pages -Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41467-021-26408-3
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Funding
- National Key Research and Development Project [2018YFC1004702]
- National Natural Science Foundation of China [31970802]
- Beijing Municipal Natural Science Foundation [7202099]
- Medical University of Bialystok, Poland [SUB/1/DN/20/006/1104]
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The research shows that NOC4L is reduced in humans and mice with obesity, and its deficiency worsens inflammation and insulin resistance induced by a high-fat diet. NOC4L interacts with Toll-like receptor 4 to inhibit endocytosis, thereby blocking TLF4/TRIF inflammatory signaling.
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.
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