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Dietary interventions are effective in body weight reduction, but not in improving insulin sensitivity and hepatic lipid mobilization. Conversely, metformin increases insulin sensitivity and promotes the inhibition of de novo hepatic lipogenesis. In this study, we evaluated the metformin effectiveness in NASH prevention and treatment, when combined with dietary intervention in male mice fed a high-fat high-sucrose diet (HFHSD). Eighty 5-week-old C57BL\/6J male mice were fed a chow or HFHSD diet and sacrificed at 20 or 40 weeks. The HFHSD-fed mice developed NASH after 20 weeks. Lipoprotein and lipidomic analyses showed that the changes associated with diet were not prevented by metformin administration. HFHSD-fed mice subject to dietary intervention combined with metformin showed a 19.6% body weight reduction compared to 9.8% in those mice subjected to dietary intervention alone. Lower hepatic steatosis scores were induced. We conclude that metformin should not be considered a preventive option for NAFLD, but it is effective in the treatment of this disorder when combined with dietary intervention.<\/jats:p>","DOI":"10.3390\/biom12121787","type":"journal-article","created":{"date-parts":[[2022,11,30]],"date-time":"2022-11-30T03:49:13Z","timestamp":1669780153000},"page":"1787","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Combining Dietary Intervention with Metformin Treatment Enhances Non-Alcoholic Steatohepatitis Remission in Mice Fed a High-Fat High-Sucrose Diet"],"prefix":"10.3390","volume":"12","author":[{"given":"Gerard","family":"Baiges-Gaya","sequence":"first","affiliation":[{"name":"Department of Medicine and Surgery, Rovira i Virgili University (URV), 43201 Reus, Spain"},{"name":"Unitat de Recerca Biom\u00e8dica (URB-CRB), Hospital Universitari de Sant Joan, Institut d\u2019Investigaci\u00f3 Santi\u00e0ria Pere i Virgili (IISPV), 43201 Reus, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabet","family":"Rodr\u00edguez-Tom\u00e0s","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, Rovira i Virgili University (URV), 43201 Reus, Spain"},{"name":"Unitat de Recerca Biom\u00e8dica (URB-CRB), Hospital Universitari de Sant Joan, Institut d\u2019Investigaci\u00f3 Santi\u00e0ria Pere i Virgili (IISPV), 43201 Reus, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8786-7368","authenticated-orcid":false,"given":"Helena","family":"Casta\u00f1\u00e9","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, Rovira i Virgili University (URV), 43201 Reus, Spain"},{"name":"Unitat de Recerca Biom\u00e8dica (URB-CRB), Hospital Universitari de Sant Joan, Institut d\u2019Investigaci\u00f3 Santi\u00e0ria Pere i Virgili (IISPV), 43201 Reus, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4251-585X","authenticated-orcid":false,"given":"Andrea","family":"Jim\u00e9nez-Franco","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, Rovira i Virgili University (URV), 43201 Reus, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N\u00faria","family":"Amig\u00f3","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, Rovira i Virgili University (URV), 43201 Reus, Spain"},{"name":"CIBER of Diabetes and Associated Metabolic Disease (CIBERDEM), ISCIII, 28029 Madrid, Spain"},{"name":"Biosfer Teslab, 43201 Reus, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3165-3640","authenticated-orcid":false,"given":"Jordi","family":"Camps","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, Rovira i Virgili University (URV), 43201 Reus, Spain"},{"name":"Unitat de Recerca Biom\u00e8dica (URB-CRB), Hospital Universitari de Sant Joan, Institut d\u2019Investigaci\u00f3 Santi\u00e0ria Pere i Virgili (IISPV), 43201 Reus, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2749-4541","authenticated-orcid":false,"given":"Jorge","family":"Joven","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, Rovira i Virgili University (URV), 43201 Reus, Spain"},{"name":"Unitat de Recerca Biom\u00e8dica (URB-CRB), Hospital Universitari de Sant Joan, Institut d\u2019Investigaci\u00f3 Santi\u00e0ria Pere i Virgili (IISPV), 43201 Reus, Spain"},{"name":"Campus of International Excellence Southern Catalonia, 43003 Tarragona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1007\/s00232-011-9401-7","article-title":"Influence of phospholipid species on membrane fluidity: A meta-analysis for a novel phospholipid fluidity index","volume":"244","author":"Fajardo","year":"2011","journal-title":"J. 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