Nonalcoholic fatty liver disease (NAFLD) is an expanding health problem worldwide. Although many studies have made great efforts to elucidate the pathogenesis of NAFLD, the molecular basis remains poorly understood. Here, we showed that hepatic C7ORF41, a critical regulator of innate immune response, was markedly decreased in diet or genetic-induced NAFLD model. We also demonstrated that C7ORF41 overexpression significantly ameliorated hepatic inflammation and lipid accumulation in palmitic acid (PA)-treated hepatocytes, whereas C7ORF41 knockdown showed the opposite effects. Mechanistically, we found the anti-inflammatory role of C7ORF41 was attributed to the suppression of NF-κB p65-mediated induction of inflammatory cytokines. Moreover, we demonstrated that the suppression of C7ORF41 expression in hepatocytes is due to JNK activation, which promotes c-Jun-mediated transcriptional repression of C7ORF41. In conclusion, our findings suggested that a c-Jun/C7ORF41/NF-κB regulatory network controls the inflammatory response and lipid accumulation in NAFLD and may benefit the development of novel and promising therapeutic targets for NAFLD.
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February 2020
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Cover Image
The cover image shows the substrate and inhibitor binding to the human biliverdin IXβ reductase active site; crystallographic structures of the ternary complexes of BLVRB with NADP+ and the substrate mesobiliverdin IVα and the inhibitor phloxine B are shown. For more information, see the article by Zhang and colleagues on pp. 601–614. Image provided by Wadie Bahou.
Research Article|
February 11 2020
C-Jun/C7ORF41/NF-κB axis mediates hepatic inflammation and lipid accumulation in NAFLD
Feng-Juan Yan
;
Feng-Juan Yan
*
1School of Life Science, Jiangsu Normal University, Xuzhou, Jiangsu, P. R. China
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Xu Wang;
Xu Wang
*
1School of Life Science, Jiangsu Normal University, Xuzhou, Jiangsu, P. R. China
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Song-En Wang;
Song-En Wang
1School of Life Science, Jiangsu Normal University, Xuzhou, Jiangsu, P. R. China
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Hai-Ting Hong;
Hai-Ting Hong
1School of Life Science, Jiangsu Normal University, Xuzhou, Jiangsu, P. R. China
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Jun Lu;
Jun Lu
1School of Life Science, Jiangsu Normal University, Xuzhou, Jiangsu, P. R. China
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Qin Ye;
Qin Ye
1School of Life Science, Jiangsu Normal University, Xuzhou, Jiangsu, P. R. China
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Yuan-Lin Zheng;
1School of Life Science, Jiangsu Normal University, Xuzhou, Jiangsu, P. R. China
2College of Health Science, Jiangsu Normal University, Xuzhou, Jiangsu, P. R. China
Correspondence: Yuan-Lin Zheng (ylzheng@jsnu.edu.cn) or Yong-Jian Wang (yjwang@jsnu.edu.cn)
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Yong-Jian Wang
1School of Life Science, Jiangsu Normal University, Xuzhou, Jiangsu, P. R. China
Correspondence: Yuan-Lin Zheng (ylzheng@jsnu.edu.cn) or Yong-Jian Wang (yjwang@jsnu.edu.cn)
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Publisher: Portland Press Ltd
Received:
October 31 2019
Revision Received:
January 17 2020
Accepted:
January 20 2020
Accepted Manuscript online:
January 20 2020
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© 2020 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society
2020
Biochem J (2020) 477 (3): 691–708.
Article history
Received:
October 31 2019
Revision Received:
January 17 2020
Accepted:
January 20 2020
Accepted Manuscript online:
January 20 2020
Citation
Feng-Juan Yan, Xu Wang, Song-En Wang, Hai-Ting Hong, Jun Lu, Qin Ye, Yuan-Lin Zheng, Yong-Jian Wang; C-Jun/C7ORF41/NF-κB axis mediates hepatic inflammation and lipid accumulation in NAFLD. Biochem J 14 February 2020; 477 (3): 691–708. doi: https://doi.org/10.1042/BCJ20190799
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