Nature Communications (Jan 2021)
Hepatocyte-specific IL11 cis-signaling drives lipotoxicity and underlies the transition from NAFLD to NASH
- 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
Affiliations
- Jinrui Dong
- Cardiovascular and Metabolic Disorders Program, Duke-National University of Singapore Medical School
- Sivakumar Viswanathan
- Cardiovascular and Metabolic Disorders Program, Duke-National University of Singapore Medical School
- Eleonora Adami
- Cardiovascular and Metabolic Disorders Program, Duke-National University of Singapore Medical School
- Brijesh K. Singh
- Cardiovascular and Metabolic Disorders Program, Duke-National University of Singapore Medical School
- Sonia P. Chothani
- Cardiovascular and Metabolic Disorders Program, Duke-National University of Singapore Medical School
- Benjamin Ng
- Cardiovascular and Metabolic Disorders Program, Duke-National University of Singapore Medical School
- Wei Wen Lim
- National Heart Research Institute Singapore, National Heart Centre Singapore
- Jin Zhou
- Cardiovascular and Metabolic Disorders Program, Duke-National University of Singapore Medical School
- Madhulika Tripathi
- Cardiovascular and Metabolic Disorders Program, Duke-National University of Singapore Medical School
- Nicole S. J. Ko
- Cardiovascular and Metabolic Disorders Program, Duke-National University of Singapore Medical School
- Shamini G. Shekeran
- Cardiovascular and Metabolic Disorders Program, Duke-National University of Singapore Medical School
- Jessie Tan
- Cardiovascular and Metabolic Disorders Program, Duke-National University of Singapore Medical School
- Sze Yun Lim
- National Heart Research Institute Singapore, National Heart Centre Singapore
- Mao Wang
- Cardiovascular and Metabolic Disorders Program, Duke-National University of Singapore Medical School
- Pei Min Lio
- National Heart Research Institute Singapore, National Heart Centre Singapore
- Paul M. Yen
- Cardiovascular and Metabolic Disorders Program, Duke-National University of Singapore Medical School
- Sebastian Schafer
- Cardiovascular and Metabolic Disorders Program, Duke-National University of Singapore Medical School
- Stuart A. Cook
- Cardiovascular and Metabolic Disorders Program, Duke-National University of Singapore Medical School
- Anissa A. Widjaja
- Cardiovascular and Metabolic Disorders Program, Duke-National University of Singapore Medical School
- DOI
- https://doi.org/10.1038/s41467-020-20303-z
- Journal volume & issue
-
Vol. 12,
no. 1
pp. 1 – 15
Abstract
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.
