Imperial College London
Alternate

ProfessorStuartCook

Faculty of Medicine, Institute of Clinical Sciences

Visiting Professor
 
 
 
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Contact

 

+44 (0)20 3313 1346stuart.cook

 
 
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Location

 

RF 16Sydney StreetRoyal Brompton Campus

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Summary

 

Publications

Citation

BibTex format

@article{Dong:2021:10.1038/s41467-020-20303-z,
author = {Dong, J and Viswanathan, S and Adami, E and Singh, BK and Chothani, SP and Ng, B and Lim, WW and Zhou, J and Tripathi, M and Ko, NSJ and Shekeran, SG and Tan, J and Lim, SY and Wang, M and Lio, PM and Yen, PM and Schafer, S and Cook, SA and Widjaja, AA},
doi = {10.1038/s41467-020-20303-z},
journal = {Nature Communications},
pages = {1--15},
title = {Hepatocyte-specific IL11 cis-signaling drives lipotoxicity and underlies the transition from NAFLD to NASH},
url = {http://dx.doi.org/10.1038/s41467-020-20303-z},
volume = {12},
year = {2021}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - IL11 is important for fibrosis in non-alcoholic steatohepatitis (NASH) but its role beyond the stroma in liver disease is unclear. Here, we investigate the role of IL11 in hepatocyte lipotoxicity. Hepatocytes highly express IL11RA and secrete IL11 in response to lipid loading. Autocrine IL11 activity causes hepatocyte death through NOX4-derived ROS, activation of ERK, JNK and caspase-3, impaired mitochondrial function and reduced fatty acid oxidation. Paracrine IL11 activity stimulates hepatic stellate cells and causes fibrosis. In mouse models of NASH, hepatocyte-specific deletion of Il11ra1 protects against liver steatosis, fibrosis and inflammation while reducing serum glucose, cholesterol and triglyceride levels and limiting obesity. In mice deleted for Il11ra1, restoration of IL11 cis-signaling in hepatocytes reconstitutes steatosis and inflammation but not fibrosis. We found no evidence for the existence of IL6 or IL11 trans-signaling in hepatocytes or NASH. These data show that IL11 modulates hepatocyte metabolism and suggests a mechanism for NAFLD to NASH transition.
AU  - Dong,J
AU  - Viswanathan,S
AU  - Adami,E
AU  - Singh,BK
AU  - Chothani,SP
AU  - Ng,B
AU  - Lim,WW
AU  - Zhou,J
AU  - Tripathi,M
AU  - Ko,NSJ
AU  - Shekeran,SG
AU  - Tan,J
AU  - Lim,SY
AU  - Wang,M
AU  - Lio,PM
AU  - Yen,PM
AU  - Schafer,S
AU  - Cook,SA
AU  - Widjaja,AA
DO  - 10.1038/s41467-020-20303-z
EP  - 15
PY  - 2021///
SN  - 2041-1723
SP  - 1
TI  - Hepatocyte-specific IL11 cis-signaling drives lipotoxicity and underlies the transition from NAFLD to NASH
T2  - Nature Communications
UR  - http://dx.doi.org/10.1038/s41467-020-20303-z
UR  - https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000665627200042&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=a2bf6146997ec60c407a63945d4e92bb
UR  - https://www.nature.com/articles/s41467-020-20303-z
UR  - http://hdl.handle.net/10044/1/105620
VL  - 12
ER  -
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