Increased hepatic putrescine levels as a new potential factor related to the progression of metabolic dysfunction-associated steatotic liver disease.
liver metabolism
metabolic dysfunction‐associated steatohepatitis
metabolic dysfunction‐associated steatotic liver disease
obesity
ornithine decarboxylase
polyamine
Journal
The Journal of pathology
ISSN: 1096-9896
Titre abrégé: J Pathol
Pays: England
ID NLM: 0204634
Informations de publication
Date de publication:
18 Jul 2024
18 Jul 2024
Historique:
revised:
05
05
2024
received:
10
01
2024
accepted:
13
06
2024
medline:
18
7
2024
pubmed:
18
7
2024
entrez:
18
7
2024
Statut:
aheadofprint
Résumé
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a chronic liver condition that often progresses to more advanced stages, such as metabolic dysfunction-associated steatohepatitis (MASH). MASH is characterized by inflammation and hepatocellular ballooning, in addition to hepatic steatosis. Despite the relatively high incidence of MASH in the population and its potential detrimental effects on human health, this liver disease is still not fully understood from a pathophysiological perspective. Deregulation of polyamine levels has been detected in various pathological conditions, including neurodegenerative diseases, inflammation, and cancer. However, the role of the polyamine pathway in chronic liver disorders such as MASLD has not been explored. In this study, we measured the expression of liver ornithine decarboxylase (ODC1), the rate-limiting enzyme responsible for the production of putrescine, and the hepatic levels of putrescine, in a preclinical model of MASH as well as in liver biopsies of patients with obesity undergoing bariatric surgery. Our findings reveal that expression of ODC1 and the levels of putrescine, but not spermidine nor spermine, are elevated in hepatic tissue of both diet-induced MASH mice and patients with biopsy-proven MASH compared with control mice and patients without MASH, respectively. Furthermore, we found that the levels of putrescine were positively associated with higher aspartate aminotransferase concentrations in serum and an increased SAF score (steatosis, activity, fibrosis). Additionally, in in vitro assays using human HepG2 cells, we demonstrate that elevated levels of putrescine exacerbate the cellular response to palmitic acid, leading to decreased cell viability and increased release of CK-18. Our results support an association between the expression of ODC1 and the progression of MASLD, which could have translational relevance in understanding the onset of this disease. © 2024 The Pathological Society of Great Britain and Ireland.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health (NIH)
ID : R01DK131038
Organisme : National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health (NIH)
ID : R03DK129419
Organisme : Instituto de Salud Carlos III
ID : CP19/00098
Organisme : Instituto de Salud Carlos III
ID : CP23/00051
Organisme : Instituto de Salud Carlos III
ID : FI21/00003
Organisme : Instituto de Salud Carlos III
ID : PI20/00505
Organisme : Instituto de Salud Carlos III
ID : PI23/00171
Informations de copyright
© 2024 The Pathological Society of Great Britain and Ireland.
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