Liver ASK1 protects from non‐alcoholic fatty liver disease and fibrosis
Abstract: Non‐alcoholic fatty liver disease (NAFLD) is strongly associated with obesity and may progress to non‐alcoholic steatohepatitis (NASH) and liver fibrosis. The deficit of pharmacological therapies for the latter mainly results from an incomplete understanding of involved pathological mechanisms. Herein, we identify apoptosis signal‐regulating kinase 1 (ASK1) as a suppressor of NASH and fibrosis formation. High‐fat diet‐fed and aged chow‐fed liver‐specific ASK1‐knockout mice develop a higher degree of hepatic steatosis, inflammation, and fibrosis compared to controls. In addition, pharmacological inhibition of ASK1 increased hepatic lipid accumulation in wild‐type mice. In line, liver‐specific ASK1 overexpression protected mice from the development of high‐fat diet‐induced hepatic steatosis and carbon tetrachloride‐induced fibrosis. Mechanistically, ASK1 depletion blunts autophagy, thereby enhancing lipid droplet accumulation and liver fibrosis. In human livers of lean and obese subjects, ASK1 expression correlated negatively with liver fat content and NASH scores, but positively with markers for autophagy. Taken together, ASK1 may be a novel therapeutic target to tackle NAFLD and liver fibrosis.
- Location
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Deutsche Nationalbibliothek Frankfurt am Main
- Extent
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Online-Ressource
- Language
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Englisch
- Bibliographic citation
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Liver ASK1 protects from non‐alcoholic fatty liver disease and fibrosis ; volume:11 ; number:10 ; year:2019 ; extent:17
EMBO molecular medicine / European Molecular Biology Organization ; 11, Heft 10 (2019) (gesamt 17)
- Creator
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Challa, Tenagne D.
Wueest, Stephan
Lucchini, Fabrizio C.
Dedual, Mara
Modica, Salvatore
Borsigova, Marcela
Wolfrum, Christian
Blüher, Matthias
Konrad, Daniel
- DOI
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10.15252/emmm.201810124
- URN
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urn:nbn:de:101:1-2022072008434821414324
- Rights
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Last update
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15.08.2025, 7:28 AM CEST
Data provider
Deutsche Nationalbibliothek. If you have any questions about the object, please contact the data provider.
Associated
- Challa, Tenagne D.
- Wueest, Stephan
- Lucchini, Fabrizio C.
- Dedual, Mara
- Modica, Salvatore
- Borsigova, Marcela
- Wolfrum, Christian
- Blüher, Matthias
- Konrad, Daniel
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