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Although a plethora of experimental models for studying NASH have been proposed, still scarce findings regarding the hepatic metabolomic\/molecular profile. In the present study, we sought to unravel the hepatic metabolomic profile of mice subjected to a hybrid model of NASH, by combining a Western diet and carbon tetrachloride administration, for 8 weeks, in male C57BL\/6J and BALB\/c mice. In both mouse strains, the main traits of NASH\u2014metabolic (glucose intolerance profile), morphologic (extensive microvesicular steatosis and fibrosis, lobular inflammation, and adipose tissue-related inflammation\/hypertrophy), and molecular (impaired Nrf2\/NF-\u03baB pathway dynamics and altered metabolomic profile)\u2014were observed. The hepatic metabolomic profile revealed that the hybrid protocol impaired, in both strains, the abundance of branched chain-aromatic amino acids, carboxylic acids, and glycosyl compounds, that might be linked to the Nrf2 pathway activation. Moreover, we observed a strain-dependent hepatic metabolomic signature, in which the tricarboxylic acid metabolites and pyruvate metabolism were dissimilarly modulated in C57BL\/6J and BALB\/c mice. Thus, we provide evidence that the strain-dependent hepatic metabolomic profile might be linked to the distinct underlying mechanisms of NASH, also prospecting potential mechanistic insights into the corresponding disease.<\/jats:p>","DOI":"10.3390\/antiox12020290","type":"journal-article","created":{"date-parts":[[2023,1,30]],"date-time":"2023-01-30T05:57:23Z","timestamp":1675058243000},"page":"290","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Unraveling Hepatic Metabolomic Profiles and Morphological Outcomes in a Hybrid Model of NASH in Different Mouse Strains"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3840-7749","authenticated-orcid":false,"given":"Gabriel P.","family":"Bacil","sequence":"first","affiliation":[{"name":"Department of Pathology, Botucatu Medical School (FMB), S\u00e3o Paulo State University (UNESP), Botucatu 18618-689, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5320-8380","authenticated-orcid":false,"given":"Guilherme R.","family":"Romualdo","sequence":"additional","affiliation":[{"name":"Department of Pathology, Botucatu Medical School (FMB), S\u00e3o Paulo State University (UNESP), Botucatu 18618-689, Brazil"},{"name":"Department of Structural and Functional Biology, Biosciences Institute, S\u00e3o Paulo State University (UNESP), Botucatu 18618-689, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priscila M. F. D.","family":"Piagge","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Molecular Physics, S\u00e3o Carlos Institute of Chemistry (IQSC), University of S\u00e3o Paulo (USP), S\u00e3o Carlos 13566-590, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3492-3327","authenticated-orcid":false,"given":"Daniel R.","family":"Cardoso","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Molecular Physics, S\u00e3o Carlos Institute of Chemistry (IQSC), University of S\u00e3o Paulo (USP), S\u00e3o Carlos 13566-590, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5115-8893","authenticated-orcid":false,"given":"Mathieu","family":"Vinken","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical and Pharmacological Sciences, University of Vrije, 1090 Brussel, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1388-7240","authenticated-orcid":false,"given":"Bruno","family":"Cogliati","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Veterinary Medicine and Animal Science, University of S\u00e3o Paulo (USP), S\u00e3o Paulo 05508-270, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2180-1814","authenticated-orcid":false,"given":"Lu\u00eds F.","family":"Barbisan","sequence":"additional","affiliation":[{"name":"Department of Structural and Functional Biology, Biosciences Institute, S\u00e3o Paulo State University (UNESP), Botucatu 18618-689, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1002\/hep.28431","article-title":"Global Epidemiology of Nonalcoholic Fatty Liver Disease\u2014Meta-Analytic Assessment of Prevalence, Incidence, and Outcomes","volume":"64","author":"Younossi","year":"2016","journal-title":"Hepatology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1053\/j.gastro.2014.11.039","article-title":"Nonalcoholic Steatohepatitis Is the Second Leading Etiology of Liver Disease among Adults Awaiting Liver Transplantation in the United States","volume":"148","author":"Wong","year":"2015","journal-title":"Gastroenterology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1016\/j.cgh.2018.05.057","article-title":"Nonalcoholic Steatohepatitis Is the Fastest Growing Cause of Hepatocellular Carcinoma in Liver Transplant Candidates","volume":"17","author":"Younossi","year":"2019","journal-title":"Clin. 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