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On the contrary, a diet enriched with n-3 polyunsaturated fatty acids (n-3-PUFAs) has been reported to ameliorate the progression of NAFLD. The aim of our study was to investigate the impact of dietary n-3-PUFA enrichment on the development of NAFLD and liver lipidome. Mice were fed for 6 weeks either a high-fat methionine choline-deficient diet (MCD) or standard chow with or without n-3-PUFAs. Liver histology, serum biochemistry, detailed plasma and liver lipidomic analyses, and genome-wide transcriptome analysis were performed. Mice fed an MCD developed histopathological changes characteristic of NAFLD, and these changes were ameliorated with n-3-PUFAs. Simultaneously, n-3-PUFAs decreased serum triacylglycerol and cholesterol concentrations as well as ALT and AST activities. N-3-PUFAs decreased serum concentrations of saturated and monounsaturated free fatty acids (FAs), while increasing serum concentrations of long-chain PUFAs. Furthermore, in the liver, the MCD significantly increased the hepatic triacylglycerol content, while the administration of n-3-PUFAs eliminated this effect. Administration of n-3-PUFAs led to significant beneficial differences in gene expression within biosynthetic pathways of cholesterol, FAs, and pro-inflammatory cytokines (IL-1 and TNF-\u03b1). To conclude, n-3-PUFA supplementation appears to represent a promising nutraceutical approach for the restoration of abnormalities in liver lipid metabolism and the prevention and treatment of NAFLD.<\/jats:p>","DOI":"10.3390\/ijms242417226","type":"journal-article","created":{"date-parts":[[2023,12,7]],"date-time":"2023-12-07T05:57:08Z","timestamp":1701928628000},"page":"17226","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["The Ameliorating Effects of n-3 Polyunsaturated Fatty Acids on Liver Steatosis Induced by a High-Fat Methionine Choline-Deficient Diet in Mice"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8664-7918","authenticated-orcid":false,"given":"V\u00e1clav","family":"\u0160m\u00edd","sequence":"first","affiliation":[{"name":"4th Department of Internal Medicine, 1st Faculty of Medicine, Charles University in Prague and General University Hospital, 128 08 Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1558-4603","authenticated-orcid":false,"given":"Karel","family":"Dvo\u0159\u00e1k","sequence":"additional","affiliation":[{"name":"4th Department of Internal Medicine, 1st Faculty of Medicine, Charles University in Prague and General University Hospital, 128 08 Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kamila","family":"Stehnov\u00e1","sequence":"additional","affiliation":[{"name":"Department of Food Analysis and Nutrition, University of Chemistry and Technology, 166 28 Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hynek","family":"Strnad","sequence":"additional","affiliation":[{"name":"Laboratory of Genomics and Bioinformatics, Institute of Molecular Genetics of the Czech Academy of Sciences, 142 20 Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1634-2334","authenticated-orcid":false,"given":"Josep","family":"Rubert","sequence":"additional","affiliation":[{"name":"Department of Food Analysis and Nutrition, University of Chemistry and Technology, 166 28 Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"St\u0159\u00edtesk\u00fd","sequence":"additional","affiliation":[{"name":"Institute of Pathology, 1st Faculty of Medicine, Charles University in Prague and General University Hospital, 128 00 Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbora","family":"Sta\u0148kov\u00e1","sequence":"additional","affiliation":[{"name":"4th Department of Internal Medicine, 1st Faculty of Medicine, Charles University in Prague and General University Hospital, 128 08 Prague, Czech Republic"},{"name":"Institute of Medical Biochemistry and Laboratory Diagnostics, 1st Faculty of Medicine, Charles University in Prague and General University Hospital, 128 08 Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milena","family":"Str\u00e1nsk\u00e1","sequence":"additional","affiliation":[{"name":"Department of Food Analysis and Nutrition, University of Chemistry and Technology, 166 28 Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jana","family":"Haj\u0161lov\u00e1","sequence":"additional","affiliation":[{"name":"Department of Food Analysis and Nutrition, University of Chemistry and Technology, 166 28 Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9924-4301","authenticated-orcid":false,"given":"Radan","family":"Br\u016fha","sequence":"additional","affiliation":[{"name":"4th Department of Internal Medicine, 1st Faculty of Medicine, Charles University in Prague and General University Hospital, 128 08 Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5318-0151","authenticated-orcid":false,"given":"Libor","family":"V\u00edtek","sequence":"additional","affiliation":[{"name":"4th Department of Internal Medicine, 1st Faculty of Medicine, Charles University in Prague and General University Hospital, 128 08 Prague, Czech Republic"},{"name":"Institute of Medical Biochemistry and Laboratory Diagnostics, 1st Faculty of Medicine, Charles University in Prague and General University Hospital, 128 08 Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,12,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1016\/j.jhep.2017.11.014","article-title":"Lipotoxicity and the gut-liver axis in NASH pathogenesis","volume":"68","author":"Marra","year":"2018","journal-title":"J. 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