Unraveling Hepatic Metabolomic Profiles and Morphological Outcomes in a Hybrid Model of NASH in Different Mouse Strains
Nonalcoholic 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 presen...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-01-01
|
| Series: | Antioxidants |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2076-3921/12/2/290 |
| _version_ | 1827758998804234240 |
|---|---|
| author | Gabriel P. Bacil Guilherme R. Romualdo Priscila M. F. D. Piagge Daniel R. Cardoso Mathieu Vinken Bruno Cogliati Luís F. Barbisan |
| author_facet | Gabriel P. Bacil Guilherme R. Romualdo Priscila M. F. D. Piagge Daniel R. Cardoso Mathieu Vinken Bruno Cogliati Luís F. Barbisan |
| author_sort | Gabriel P. Bacil |
| collection | DOAJ |
| description | Nonalcoholic 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. |
| first_indexed | 2024-03-11T09:14:30Z |
| format | Article |
| id | doaj.art-e81b690938a34519a6896a5e02243215 |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-11T09:14:30Z |
| publishDate | 2023-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-e81b690938a34519a6896a5e022432152023-11-16T18:46:05ZengMDPI AGAntioxidants2076-39212023-01-0112229010.3390/antiox12020290Unraveling Hepatic Metabolomic Profiles and Morphological Outcomes in a Hybrid Model of NASH in Different Mouse StrainsGabriel P. Bacil0Guilherme R. Romualdo1Priscila M. F. D. Piagge2Daniel R. Cardoso3Mathieu Vinken4Bruno Cogliati5Luís F. Barbisan6Department of Pathology, Botucatu Medical School (FMB), São Paulo State University (UNESP), Botucatu 18618-689, BrazilDepartment of Pathology, Botucatu Medical School (FMB), São Paulo State University (UNESP), Botucatu 18618-689, BrazilDepartment of Chemistry and Molecular Physics, São Carlos Institute of Chemistry (IQSC), University of São Paulo (USP), São Carlos 13566-590, BrazilDepartment of Chemistry and Molecular Physics, São Carlos Institute of Chemistry (IQSC), University of São Paulo (USP), São Carlos 13566-590, BrazilDepartment of Pharmaceutical and Pharmacological Sciences, University of Vrije, 1090 Brussel, BelgiumDepartment of Pathology, School of Veterinary Medicine and Animal Science, University of São Paulo (USP), São Paulo 05508-270, BrazilDepartment of Structural and Functional Biology, Biosciences Institute, São Paulo State University (UNESP), Botucatu 18618-689, BrazilNonalcoholic 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.https://www.mdpi.com/2076-3921/12/2/290nonalcoholic fatty liver diseasenonalcoholic steatohepatitismetabolomic profilewestern dietcarbon tetrachloride |
| spellingShingle | Gabriel P. Bacil Guilherme R. Romualdo Priscila M. F. D. Piagge Daniel R. Cardoso Mathieu Vinken Bruno Cogliati Luís F. Barbisan Unraveling Hepatic Metabolomic Profiles and Morphological Outcomes in a Hybrid Model of NASH in Different Mouse Strains Antioxidants nonalcoholic fatty liver disease nonalcoholic steatohepatitis metabolomic profile western diet carbon tetrachloride |
| title | Unraveling Hepatic Metabolomic Profiles and Morphological Outcomes in a Hybrid Model of NASH in Different Mouse Strains |
| title_full | Unraveling Hepatic Metabolomic Profiles and Morphological Outcomes in a Hybrid Model of NASH in Different Mouse Strains |
| title_fullStr | Unraveling Hepatic Metabolomic Profiles and Morphological Outcomes in a Hybrid Model of NASH in Different Mouse Strains |
| title_full_unstemmed | Unraveling Hepatic Metabolomic Profiles and Morphological Outcomes in a Hybrid Model of NASH in Different Mouse Strains |
| title_short | Unraveling Hepatic Metabolomic Profiles and Morphological Outcomes in a Hybrid Model of NASH in Different Mouse Strains |
| title_sort | unraveling hepatic metabolomic profiles and morphological outcomes in a hybrid model of nash in different mouse strains |
| topic | nonalcoholic fatty liver disease nonalcoholic steatohepatitis metabolomic profile western diet carbon tetrachloride |
| url | https://www.mdpi.com/2076-3921/12/2/290 |
| work_keys_str_mv | AT gabrielpbacil unravelinghepaticmetabolomicprofilesandmorphologicaloutcomesinahybridmodelofnashindifferentmousestrains AT guilhermerromualdo unravelinghepaticmetabolomicprofilesandmorphologicaloutcomesinahybridmodelofnashindifferentmousestrains AT priscilamfdpiagge unravelinghepaticmetabolomicprofilesandmorphologicaloutcomesinahybridmodelofnashindifferentmousestrains AT danielrcardoso unravelinghepaticmetabolomicprofilesandmorphologicaloutcomesinahybridmodelofnashindifferentmousestrains AT mathieuvinken unravelinghepaticmetabolomicprofilesandmorphologicaloutcomesinahybridmodelofnashindifferentmousestrains AT brunocogliati unravelinghepaticmetabolomicprofilesandmorphologicaloutcomesinahybridmodelofnashindifferentmousestrains AT luisfbarbisan unravelinghepaticmetabolomicprofilesandmorphologicaloutcomesinahybridmodelofnashindifferentmousestrains |