Hepatocyte-specific IL11 cis-signaling drives lipotoxicity and underlies the transition from NAFLD to NASH

IL11 contributes to the development of non-alcoholic steatohepatitis (NASH) through incompletely understood mechanisms. Here, the authors report that lipotoxicity-driven autocrine IL11 activity underlies hepatocyte metabolic dysfunction and death via a NOX4/ERK-mediated mechanism while paracrine IL1...

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Main Authors:	Jinrui Dong, Sivakumar Viswanathan, Eleonora Adami, Brijesh K. Singh, Sonia P. Chothani, Benjamin Ng, Wei Wen Lim, Jin Zhou, Madhulika Tripathi, Nicole S. J. Ko, Shamini G. Shekeran, Jessie Tan, Sze Yun Lim, Mao Wang, Pei Min Lio, Paul M. Yen, Sebastian Schafer, Stuart A. Cook, Anissa A. Widjaja
Format:	Article
Language:	English
Published:	Nature Publishing Group 2021-01-01
Series:	Nature Communications
Online Access:	https://doi.org/10.1038/s41467-020-20303-z

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spelling	doaj-ce2b5ee017d5453ea86274564e8eb24f2021-01-10T12:18:22ZengNature Publishing GroupNature Communications2041-17232021-01-0112111510.1038/s41467-020-20303-zHepatocyte-specific IL11 cis-signaling drives lipotoxicity and underlies the transition from NAFLD to NASHJinrui Dong0Sivakumar Viswanathan1Eleonora Adami2Brijesh K. Singh3Sonia P. Chothani4Benjamin Ng5Wei Wen Lim6Jin Zhou7Madhulika Tripathi8Nicole S. J. Ko9Shamini G. Shekeran10Jessie Tan11Sze Yun Lim12Mao Wang13Pei Min Lio14Paul M. Yen15Sebastian Schafer16Stuart A. Cook17Anissa A. Widjaja18Cardiovascular and Metabolic Disorders Program, Duke-National University of Singapore Medical SchoolCardiovascular and Metabolic Disorders Program, Duke-National University of Singapore Medical SchoolCardiovascular and Metabolic Disorders Program, Duke-National University of Singapore Medical SchoolCardiovascular and Metabolic Disorders Program, Duke-National University of Singapore Medical SchoolCardiovascular and Metabolic Disorders Program, Duke-National University of Singapore Medical SchoolCardiovascular and Metabolic Disorders Program, Duke-National University of Singapore Medical SchoolNational Heart Research Institute Singapore, National Heart Centre SingaporeCardiovascular and Metabolic Disorders Program, Duke-National University of Singapore Medical SchoolCardiovascular and Metabolic Disorders Program, Duke-National University of Singapore Medical SchoolCardiovascular and Metabolic Disorders Program, Duke-National University of Singapore Medical SchoolCardiovascular and Metabolic Disorders Program, Duke-National University of Singapore Medical SchoolCardiovascular and Metabolic Disorders Program, Duke-National University of Singapore Medical SchoolNational Heart Research Institute Singapore, National Heart Centre SingaporeCardiovascular and Metabolic Disorders Program, Duke-National University of Singapore Medical SchoolNational Heart Research Institute Singapore, National Heart Centre SingaporeCardiovascular and Metabolic Disorders Program, Duke-National University of Singapore Medical SchoolCardiovascular and Metabolic Disorders Program, Duke-National University of Singapore Medical SchoolCardiovascular and Metabolic Disorders Program, Duke-National University of Singapore Medical SchoolCardiovascular and Metabolic Disorders Program, Duke-National University of Singapore Medical SchoolIL11 contributes to the development of non-alcoholic steatohepatitis (NASH) through incompletely understood mechanisms. Here, the authors report that lipotoxicity-driven autocrine IL11 activity underlies hepatocyte metabolic dysfunction and death via a NOX4/ERK-mediated mechanism while paracrine IL11 activity stimulates hepatic stellate cells contributing to fibrosis and inflammation in the context of NASH.https://doi.org/10.1038/s41467-020-20303-z
collection	DOAJ
language	English
format	Article
sources	DOAJ
author	Jinrui Dong Sivakumar Viswanathan Eleonora Adami Brijesh K. Singh Sonia P. Chothani Benjamin Ng Wei Wen Lim Jin Zhou Madhulika Tripathi Nicole S. J. Ko Shamini G. Shekeran Jessie Tan Sze Yun Lim Mao Wang Pei Min Lio Paul M. Yen Sebastian Schafer Stuart A. Cook Anissa A. Widjaja
spellingShingle	Jinrui Dong Sivakumar Viswanathan Eleonora Adami Brijesh K. Singh Sonia P. Chothani Benjamin Ng Wei Wen Lim Jin Zhou Madhulika Tripathi Nicole S. J. Ko Shamini G. Shekeran Jessie Tan Sze Yun Lim Mao Wang Pei Min Lio Paul M. Yen Sebastian Schafer Stuart A. Cook Anissa A. Widjaja Hepatocyte-specific IL11 cis-signaling drives lipotoxicity and underlies the transition from NAFLD to NASH Nature Communications
author_facet	Jinrui Dong Sivakumar Viswanathan Eleonora Adami Brijesh K. Singh Sonia P. Chothani Benjamin Ng Wei Wen Lim Jin Zhou Madhulika Tripathi Nicole S. J. Ko Shamini G. Shekeran Jessie Tan Sze Yun Lim Mao Wang Pei Min Lio Paul M. Yen Sebastian Schafer Stuart A. Cook Anissa A. Widjaja
author_sort	Jinrui Dong
title	Hepatocyte-specific IL11 cis-signaling drives lipotoxicity and underlies the transition from NAFLD to NASH
title_short	Hepatocyte-specific IL11 cis-signaling drives lipotoxicity and underlies the transition from NAFLD to NASH
title_full	Hepatocyte-specific IL11 cis-signaling drives lipotoxicity and underlies the transition from NAFLD to NASH
title_fullStr	Hepatocyte-specific IL11 cis-signaling drives lipotoxicity and underlies the transition from NAFLD to NASH
title_full_unstemmed	Hepatocyte-specific IL11 cis-signaling drives lipotoxicity and underlies the transition from NAFLD to NASH
title_sort	hepatocyte-specific il11 cis-signaling drives lipotoxicity and underlies the transition from nafld to nash
publisher	Nature Publishing Group
series	Nature Communications
issn	2041-1723
publishDate	2021-01-01
description	IL11 contributes to the development of non-alcoholic steatohepatitis (NASH) through incompletely understood mechanisms. Here, the authors report that lipotoxicity-driven autocrine IL11 activity underlies hepatocyte metabolic dysfunction and death via a NOX4/ERK-mediated mechanism while paracrine IL11 activity stimulates hepatic stellate cells contributing to fibrosis and inflammation in the context of NASH.
url	https://doi.org/10.1038/s41467-020-20303-z
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Hepatocyte-specific IL11 cis-signaling drives lipotoxicity and underlies the transition from NAFLD to NASH

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