Oxidative stress in metabolic dysfunction-associated steatotic liver disease (MASLD): How does the animal model resemble human disease?
antioxidant defense system
mitochondrial respiratory chain
obese patients
oxidative damage
reactive oxygen species
Journal
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
ISSN: 1530-6860
Titre abrégé: FASEB J
Pays: United States
ID NLM: 8804484
Informations de publication
Date de publication:
15 Feb 2024
15 Feb 2024
Historique:
revised:
15
01
2024
received:
28
11
2023
accepted:
22
01
2024
medline:
6
2
2024
pubmed:
6
2
2024
entrez:
6
2
2024
Statut:
ppublish
Résumé
Despite decades of research, the pathogenesis of metabolic dysfunction-associated steatotic liver disease (MASLD) is still not completely understood. Based on the evidence from preclinical models, one of the factors proposed as a main driver of disease development is oxidative stress. This study aimed to search for the resemblance between the profiles of oxidative stress and antioxidant defense in the animal model of MASLD and the group of MASLD patients. C57BL/6J mice were fed with the Western diet for up to 24 weeks and served as the animal model of MASLD. The antioxidant profile of mice hepatic tissue was determined by liquid chromatography-MS3 spectrometry (LC-MS/MS). The human cohort consisted of 20 patients, who underwent bariatric surgery, and 6 controls. Based on histological analysis, 4 bariatric patients did not have liver steatosis and as such were also classified as controls. Total antioxidant activity was measured in sera and liver biopsy samples. The hepatic levels of antioxidant enzymes and oxidative damage were determined by Western Blot. The levels of antioxidant enzymes were significantly altered in the hepatic tissue of mice with MASLD. In contrast, there were no significant changes in the antioxidant profile of hepatic tissue of MASLD patients, except for the decreased level of carbonylated proteins. Decreased protein carbonylation together with significant correlations between the thioredoxin system and parameters describing metabolic health suggest alterations in the thiol-redox signaling. Altogether, these data show that even though the phenotype of mice closely resembles human MASLD, the animal-to-human translation of cellular and molecular processes such as oxidative stress may be more challenging.
Identifiants
pubmed: 38318780
doi: 10.1096/fj.202302447R
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e23466Subventions
Organisme : Fondazione AIRC per la ricerca sul cancro ETS (AIRC)
ID : AIRC,IG-23670
Organisme : Ministero dell'Università e della Ricerca (MUR)
ID : PRIN,2017 E5L5P3
Organisme : EC | HORIZON EUROPE Framework Programme (Horizon Europe)
ID : 101080329
Organisme : Narodowe Centrum Nauki (NCN)
ID : UMO-2021/43/I/NZ3/00510
Organisme : Narodowe Centrum Nauki (NCN)
ID : UMO-2018/29/B/NZ1/00589
Informations de copyright
© 2024 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.
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