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Multiple omics study identifies an interspecies conserved driver for nonalcoholic steatohepatitis.

Publication ,  Journal Article
Zhang, X-J; She, Z-G; Wang, J; Sun, D; Shen, L-J; Xiang, H; Cheng, X; Ji, Y-X; Huang, Y-P; Li, P-L; Yang, X; Cheng, Y; Ma, J-P; Wang, H-P ...
Published in: Sci Transl Med
December 15, 2021

Lipotoxicity is a recognized pathological trigger and accelerator of nonalcoholic steatohepatitis (NASH). However, the molecular basis of lipotoxicity-induced NASH remains elusive. Here, we systematically mapped the changes in hepatic transcriptomic landscapes in response to lipotoxic insults across multiple species. Conserved and robust activation of the arachidonic acid pathway, in particular the arachidonate 12-lipoxygenase (ALOX12) gene, was closely correlated with NASH severity in humans, macaques with spontaneously developed NASH, as well as swine and mouse dietary NASH models. Using gain- and loss-of-function studies, we found that ALOX12 markedly exacerbated NASH in both mice and Bama pig models. ALOX12 was shown to induce NASH by directly targeting acetyl-CoA carboxylase 1 (ACC1) via a lysosomal degradation mechanism. Overall, our findings reveal a key molecular driver of NASH pathogenesis and suggest that ALOX12-ACC1 interaction may be a therapeutic target in NASH.

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Published In

Sci Transl Med

DOI

EISSN

1946-6242

Publication Date

December 15, 2021

Volume

13

Issue

624

Start / End Page

eabg8117

Location

United States

Related Subject Headings

  • Swine
  • Non-alcoholic Fatty Liver Disease
  • Mice, Inbred C57BL
  • Mice
  • Liver Cirrhosis
  • Liver
  • Disease Models, Animal
  • Animals
  • 4003 Biomedical engineering
  • 3206 Medical biotechnology
 

Citation

APA
Chicago
ICMJE
MLA
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Zhang, X.-J., She, Z.-G., Wang, J., Sun, D., Shen, L.-J., Xiang, H., … Li, H. (2021). Multiple omics study identifies an interspecies conserved driver for nonalcoholic steatohepatitis. Sci Transl Med, 13(624), eabg8117. https://doi.org/10.1126/scitranslmed.abg8117
Zhang, Xiao-Jing, Zhi-Gang She, Junyong Wang, Dating Sun, Li-Jun Shen, Hui Xiang, Xu Cheng, et al. “Multiple omics study identifies an interspecies conserved driver for nonalcoholic steatohepatitis.Sci Transl Med 13, no. 624 (December 15, 2021): eabg8117. https://doi.org/10.1126/scitranslmed.abg8117.
Zhang X-J, She Z-G, Wang J, Sun D, Shen L-J, Xiang H, et al. Multiple omics study identifies an interspecies conserved driver for nonalcoholic steatohepatitis. Sci Transl Med. 2021 Dec 15;13(624):eabg8117.
Zhang, Xiao-Jing, et al. “Multiple omics study identifies an interspecies conserved driver for nonalcoholic steatohepatitis.Sci Transl Med, vol. 13, no. 624, Dec. 2021, p. eabg8117. Pubmed, doi:10.1126/scitranslmed.abg8117.
Zhang X-J, She Z-G, Wang J, Sun D, Shen L-J, Xiang H, Cheng X, Ji Y-X, Huang Y-P, Li P-L, Yang X, Cheng Y, Ma J-P, Wang H-P, Hu Y, Hu F, Tian S, Tian H, Zhang P, Zhao G-N, Wang L, Hu M-L, Yang Q, Zhu L-H, Cai J, Yang J, Zhang X, Ma X, Xu Q, Touyz RM, Liu PP, Loomba R, Wang Y, Li H. Multiple omics study identifies an interspecies conserved driver for nonalcoholic steatohepatitis. Sci Transl Med. 2021 Dec 15;13(624):eabg8117.

Published In

Sci Transl Med

DOI

EISSN

1946-6242

Publication Date

December 15, 2021

Volume

13

Issue

624

Start / End Page

eabg8117

Location

United States

Related Subject Headings

  • Swine
  • Non-alcoholic Fatty Liver Disease
  • Mice, Inbred C57BL
  • Mice
  • Liver Cirrhosis
  • Liver
  • Disease Models, Animal
  • Animals
  • 4003 Biomedical engineering
  • 3206 Medical biotechnology