Unraveling Hepatic Metabolomic Profiles and Morphological Outcomes in a Hybrid Model of NASH in Different Mouse Strains

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dc.contributor.authorBacil, Gabriel P. [UNESP]
dc.contributor.authorRomualdo, Guilherme R. [UNESP]
dc.contributor.authorPiagge, Priscila M. F. D.
dc.contributor.authorCardoso, Daniel R.
dc.contributor.authorVinken, Mathieu
dc.contributor.authorCogliati, Bruno
dc.contributor.authorBarbisan, Luís F. [UNESP]
dc.contributor.institutionUniversidade Estadual Paulista (UNESP)
dc.contributor.institutionUniversidade de São Paulo (USP)
dc.contributor.institutionUniversity of Vrije
dc.date.accessioned2023-07-29T13:44:16Z
dc.date.available2023-07-29T13:44:16Z
dc.date.issued2023-02-01
dc.description.abstractNonalcoholic fatty liver disease (NAFLD) encompasses nonalcoholic steatohepatitis (NASH) and affects 25% of the global population. 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—metabolic (glucose intolerance profile), morphologic (extensive microvesicular steatosis and fibrosis, lobular inflammation, and adipose tissue-related inflammation/hypertrophy), and molecular (impaired Nrf2/NF-κB pathway dynamics and altered metabolomic profile)—were 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.en
dc.description.affiliationDepartment of Pathology Botucatu Medical School (FMB) São Paulo State University (UNESP)
dc.description.affiliationDepartment of Structural and Functional Biology Biosciences Institute São Paulo State University (UNESP)
dc.description.affiliationDepartment of Chemistry and Molecular Physics São Carlos Institute of Chemistry (IQSC) University of São Paulo (USP)
dc.description.affiliationDepartment of Pharmaceutical and Pharmacological Sciences University of Vrije
dc.description.affiliationDepartment of Pathology School of Veterinary Medicine and Animal Science University of São Paulo (USP)
dc.description.affiliationUnespDepartment of Pathology Botucatu Medical School (FMB) São Paulo State University (UNESP)
dc.description.affiliationUnespDepartment of Structural and Functional Biology Biosciences Institute São Paulo State University (UNESP)
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.description.sponsorshipIdFAPESP: #2017/01189-0
dc.description.sponsorshipIdFAPESP: #2020/01078-7
dc.description.sponsorshipIdCNPq: #309212/2019-7
dc.identifierhttp://dx.doi.org/10.3390/antiox12020290
dc.identifier.citationAntioxidants, v. 12, n. 2, 2023.
dc.identifier.doi10.3390/antiox12020290
dc.identifier.issn2076-3921
dc.identifier.scopus2-s2.0-85149211401
dc.identifier.urihttp://hdl.handle.net/11449/248444
dc.language.isoeng
dc.relation.ispartofAntioxidants
dc.sourceScopus
dc.subjectcarbon tetrachloride
dc.subjectmetabolomic profile
dc.subjectnonalcoholic fatty liver disease
dc.subjectnonalcoholic steatohepatitis
dc.subjectwestern diet
dc.titleUnraveling Hepatic Metabolomic Profiles and Morphological Outcomes in a Hybrid Model of NASH in Different Mouse Strainsen
dc.typeArtigo
unesp.author.orcid0000-0003-3840-7749[1]
unesp.author.orcid0000-0001-5320-8380[2]
unesp.author.orcid0000-0002-3492-3327[4]
unesp.author.orcid0000-0001-5115-8893[5]
unesp.author.orcid0000-0002-1388-7240[6]
unesp.author.orcid0000-0002-2180-1814[7]

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