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Although its utility in the prevention and management of a wide range of vascular disorders, including type 2 diabetes and metabolic syndrome has been suggested before, the potential of salsalate to protect against non\u2010alcoholic steatohepatitis (NASH) remains unclear. The aim of the present study was therefore to ascertain the effects of salsalate on the development of NASH.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>Transgenic APOE*3Leiden.CETP mice were fed a high\u2010fat and high\u2010cholesterol diet with or without salsalate for 12 and 20 weeks. The effects on body weight, plasma biochemical variables, liver histology and hepatic gene expression were assessed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Salsalate prevented weight gain, improved dyslipidemia and insulin resistance and ameliorated diet\u2010induced NASH, as shown by decreased hepatic microvesicular and macrovesicular steatosis, reduced hepatic inflammation and reduced development of fibrosis. Salsalate affected lipid metabolism by increasing \u03b2\u2010oxidation and decreasing lipogenesis, as shown by the activation of PPAR\u2010\u03b1, PPAR\u2010\u03b3 co\u2010activator 1\u03b2, RXR\u2010\u03b1 and inhibition of genes controlled by the transcription factor MLXIPL\/ChREBP. Inflammation was reduced by down\u2010regulation of the NF\u2010\u03baB pathway, and fibrosis development was prevented by down\u2010regulation of TGF\u2010\u03b2 signalling.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications<\/jats:title><jats:p>Salsalate exerted a preventive effect on the development of NASH and progression to fibrosis. These data suggest a clinical application of salsalate in preventing NASH.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.13315","type":"journal-article","created":{"date-parts":[[2015,8,21]],"date-time":"2015-08-21T06:07:25Z","timestamp":1440137245000},"page":"5293-5305","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Salsalate attenuates diet induced non\u2010alcoholic steatohepatitis in mice by decreasing lipogenic and inflammatory processes"],"prefix":"10.1111","volume":"172","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1412-6507","authenticated-orcid":false,"given":"Wen","family":"Liang","sequence":"first","affiliation":[{"name":"Department of Metabolic Health Research The Netherlands Organization for Applied Scientific Research (TNO)  Leiden The Netherlands"},{"name":"Department of Endocrinology and Metabolic Diseases Leiden University Medical Center  Leiden The 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