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We investigated whether a selective COX\u20102 inhibitor, celecoxib, alleviates hepatic steatosis by targeting an Akt\u2010driven lipogenic pathway. We estimated the efficacy of celecoxib in a novel Akt\u2010driven NAFLD mouse model established via hydrodynamic transfection of activated forms of AKT and in fructose\u2010fed NAFLD mice that exhibited increased insulin\u2010independent hepatic lipogenesis. AKT\u2010transfected and insulin\u2010stimulated human hepatoma cells were used for the in vitro experiments. Haematoxylin and eosin staining, immunohistochemistry and immunoblotting were performed for mechanistic studies. The results revealed that celecoxib ameliorated hepatic steatosis in the AKT\u2010triggered NAFLD mice. Mechanistically, celecoxib effectively suppressed AKT\/mTORC1 signalling and its downstream lipogenic cascade in the Akt\u2010driven NAFLD mice and in vitro. Furthermore, celecoxib had limited efficacy in alleviating hepatic lipid accumulation and showed no influence on lipogenic proteins associated with hepatic lipogenesis in fructose\u2010administered mice. This study suggests that celecoxib may be favourable for the treatment of NAFLD, especially in the subset with Akt\u2010triggered hepatic lipogenesis.<\/jats:p>","DOI":"10.1111\/jcmm.17435","type":"journal-article","created":{"date-parts":[[2022,6,17]],"date-time":"2022-06-17T05:40:10Z","timestamp":1655444410000},"page":"3995-4006","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Celecoxib attenuates hepatosteatosis by impairing de novo lipogenesis via Akt\u2010dependent lipogenic pathway"],"prefix":"10.1111","volume":"26","author":[{"given":"Cong","family":"Zhang","sequence":"first","affiliation":[{"name":"College of Pharmacy Hubei University of Chinese Medicine  Wuhan People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuzhen","family":"Lu","sequence":"additional","affiliation":[{"name":"College of Pharmacy Hubei University of Chinese Medicine  Wuhan People's Republic of 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