UM
Hepatocyte TRAF3 promotes liver steatosis and systemic insulin resistance through targeting TAK1-dependent signalling
Wang P.-X.; Zhang X.-J.; Luo P.; Jiang X.; Zhang P.; Guo J.; Zhao G.-N.; Zhu X.; Zhang Y.; Yang S.; Li H.
2016
Source PublicationNature Communications
ISSN20411723
Volume7
AbstractNon-alcoholic fatty liver disease (NAFLD) is characterized by hepatic steatosis, insulin resistance and a systemic pro-inflammatory response. Here we show that tumour necrosis factor receptor-associated factor 3 (TRAF3) is upregulated in mouse and human livers with hepatic steatosis. After 24 weeks on a high-fat diet (HFD), obesity, insulin resistance, hepatic steatosis and inflammatory responses are significantly ameliorated in liver-specific TRAF3-knockout mice, but exacerbated in transgenic mice overexpressing TRAF3 in hepatocytes. The detrimental effects of TRAF3 on hepatic steatosis and related pathologies are confirmed in ob/ob mice. We further show that in response to HFD, hepatocyte TRAF3 binds to TGF-β-activated kinase 1 (TAK1) to induce TAK1 ubiquitination and subsequent autophosphorylation, thereby enhancing the activation of downstream IKKβ-NF-κB and MKK-JNK-IRS1 307 signalling cascades, while disrupting AKT-GSK3β/FOXO1 signalling. The TRAF3-TAK1 interaction and TAK1 ubiquitination are indispensable for TRAF3-regulated hepatic steatosis. In conclusion, hepatocyte TRAF3 promotes HFD-induced or genetic hepatic steatosis in a TAK1-dependent manner.
DOI10.1038/ncomms10592
URLView the original
Language英语
The Source to ArticleScopus
Fulltext Access
Citation statistics
Cited Times [WOS]:42   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionUniversity of Macau
Recommended Citation
GB/T 7714
Wang P.-X.,Zhang X.-J.,Luo P.,et al. Hepatocyte TRAF3 promotes liver steatosis and systemic insulin resistance through targeting TAK1-dependent signalling[J]. Nature Communications,2016,7.
APA Wang P.-X..,Zhang X.-J..,Luo P..,Jiang X..,Zhang P..,...&Li H..(2016).Hepatocyte TRAF3 promotes liver steatosis and systemic insulin resistance through targeting TAK1-dependent signalling.Nature Communications,7.
MLA Wang P.-X.,et al."Hepatocyte TRAF3 promotes liver steatosis and systemic insulin resistance through targeting TAK1-dependent signalling".Nature Communications 7(2016).
Related Services
Recommend this item
Bookmark
Usage statistics
Export to Endnote
Google Scholar
Similar articles in Google Scholar
[Wang P.-X.]'s Articles
[Zhang X.-J.]'s Articles
[Luo P.]'s Articles
Baidu academic
Similar articles in Baidu academic
[Wang P.-X.]'s Articles
[Zhang X.-J.]'s Articles
[Luo P.]'s Articles
Bing Scholar
Similar articles in Bing Scholar
[Wang P.-X.]'s Articles
[Zhang X.-J.]'s Articles
[Luo P.]'s Articles
Terms of Use
No data!
Social Bookmark/Share
All comments (0)
No comment.
 

Items in the repository are protected by copyright, with all rights reserved, unless otherwise indicated.