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Antioxidants
Volume 12
Issue 2
10.3390/antiox12020290
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Article

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

by
Gabriel P. Bacil
1,
Guilherme R. Romualdo
1,2,
Priscila M. F. D. Piagge
3,
Daniel R. Cardoso
3,
Mathieu Vinken
4,
Bruno Cogliati
5 and
Luís F. Barbisan
2,*
1
Department of Pathology, Botucatu Medical School (FMB), São Paulo State University (UNESP), Botucatu 18618-689, Brazil
2
Department of Structural and Functional Biology, Biosciences Institute, São Paulo State University (UNESP), Botucatu 18618-689, Brazil
3
Department of Chemistry and Molecular Physics, São Carlos Institute of Chemistry (IQSC), University of São Paulo (USP), São Carlos 13566-590, Brazil
4
Department of Pharmaceutical and Pharmacological Sciences, University of Vrije, 1090 Brussel, Belgium
5
Department of Pathology, School of Veterinary Medicine and Animal Science, University of São Paulo (USP), São Paulo 05508-270, Brazil
*
Author to whom correspondence should be addressed.
Antioxidants 2023, 12(2), 290; https://doi.org/10.3390/antiox12020290
Submission received: 7 November 2022 / Revised: 27 December 2022 / Accepted: 29 December 2022 / Published: 27 January 2023
(This article belongs to the Special Issue Oxidative Stress as a Crucial Factor in Liver Diseases: From Basic Research to Clinical Trials)
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Abstract

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.
Keywords: nonalcoholic fatty liver disease; nonalcoholic steatohepatitis; metabolomic profile; western diet; carbon tetrachloride nonalcoholic fatty liver disease; nonalcoholic steatohepatitis; metabolomic profile; western diet; carbon tetrachloride

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MDPI and ACS Style

Bacil, G.P.; Romualdo, G.R.; Piagge, P.M.F.D.; Cardoso, D.R.; Vinken, M.; Cogliati, B.; Barbisan, L.F. Unraveling Hepatic Metabolomic Profiles and Morphological Outcomes in a Hybrid Model of NASH in Different Mouse Strains. Antioxidants 2023, 12, 290. https://doi.org/10.3390/antiox12020290

AMA Style

Bacil GP, Romualdo GR, Piagge PMFD, Cardoso DR, Vinken M, Cogliati B, Barbisan LF. Unraveling Hepatic Metabolomic Profiles and Morphological Outcomes in a Hybrid Model of NASH in Different Mouse Strains. Antioxidants. 2023; 12(2):290. https://doi.org/10.3390/antiox12020290

Chicago/Turabian Style

Bacil, Gabriel P., Guilherme R. Romualdo, Priscila M. F. D. Piagge, Daniel R. Cardoso, Mathieu Vinken, Bruno Cogliati, and Luís F. Barbisan. 2023. "Unraveling Hepatic Metabolomic Profiles and Morphological Outcomes in a Hybrid Model of NASH in Different Mouse Strains" Antioxidants 12, no. 2: 290. https://doi.org/10.3390/antiox12020290

APA Style

Bacil, G. P., Romualdo, G. R., Piagge, P. M. F. D., Cardoso, D. R., Vinken, M., Cogliati, B., & Barbisan, L. F. (2023). Unraveling Hepatic Metabolomic Profiles and Morphological Outcomes in a Hybrid Model of NASH in Different Mouse Strains. Antioxidants, 12(2), 290. https://doi.org/10.3390/antiox12020290

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