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After 12\u2010week NASH modeling, hyperammonemia was induced by intragastric administration of ammonium chloride solution (NH<jats:sub>4<\/jats:sub>Cl) or liver\u2010specific carbamoyl phosphate synthetase 1 (<jats:italic>Cps1<\/jats:italic>) knockdown. In vitro experiments were performed in HepG2 cells induced by free fatty acid (FFA) and NH<jats:sub>4<\/jats:sub>Cl.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>NH<jats:sub>4<\/jats:sub>Cl administration led to increased levels of plasma and hepatic ammonia in NASH mice. NH<jats:sub>4<\/jats:sub>Cl\u2010induced hyperammonemia did not influence liver histological changes in mice fed with HFD; however, elevated plasma cholesterol level, and an increasing trend of liver lipid content were observed. No significant effect of hyperammonemia on hepatic inflammation and fibrosis in NASH mice was found. In vitro cell experiments showed that NH<jats:sub>4<\/jats:sub>Cl treatment failed to increase the lipid droplet content and the expressions of de novo lipogenesis genes in HepG2 cells induced by FFA. The knockdown of <jats:italic>Cps1<\/jats:italic> in HFD\u2010fed mice resulted in elevated plasma ammonia levels but did not cause histological change in the liver.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our study revealed a limited role of ammonia in aggravating the progression of NASH. Further studies are needed to clarify the role and mechanism of ammonia in NASH development.<\/jats:p><\/jats:sec>","DOI":"10.1111\/1751-2980.13214","type":"journal-article","created":{"date-parts":[[2023,8,2]],"date-time":"2023-08-02T08:33:31Z","timestamp":1690965211000},"page":"408-418","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Limited role for hyperammonemia in the progression of diet\u2010induced nonalcoholic steatohepatitis"],"prefix":"10.1111","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4625-946X","authenticated-orcid":false,"given":"Zi Xuan","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Gastroenterology Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2994-1264","authenticated-orcid":false,"given":"Meng 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