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The deficit of pharmacological therapies for the latter mainly results from an incomplete understanding of involved pathological mechanisms. Herein, we identify apoptosis signal\u2010regulating kinase 1 (ASK1) as a suppressor of NASH and fibrosis formation. High\u2010fat diet\u2010fed and aged chow\u2010fed liver\u2010specific ASK1\u2010knockout 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\u2010type mice. In line, liver\u2010specific ASK1 overexpression protected mice from the development of high\u2010fat diet\u2010induced hepatic steatosis and carbon tetrachloride\u2010induced 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.<\/jats:p>","DOI":"10.15252\/emmm.201810124","type":"journal-article","created":{"date-parts":[[2019,6,6]],"date-time":"2019-06-06T17:25:14Z","timestamp":1559841914000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":75,"title":["Liver ASK1 protects from non\u2010alcoholic fatty liver disease and fibrosis"],"prefix":"10.1038","volume":"11","author":[{"given":"Tenagne D","family":"Challa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"Wueest","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabrizio C","family":"Lucchini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mara","family":"Dedual","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salvatore","family":"Modica","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcela","family":"Borsigova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Wolfrum","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Bl\u00fcher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5898-8061","authenticated-orcid":false,"given":"Daniel","family":"Konrad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,6,6]]},"reference":[{"key":"BFEMMM201810124_CR1","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1016\/j.jhep.2019.01.026","volume":"70","author":"M Allaire","year":"2019","unstructured":"Allaire M, Rautou PE, Codogno P, Lotersztajn S (2019) Autophagy in liver diseases: time for translation? 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