Pirfenidone prevents and reverses hepatic insulin resistance and steatohepatitis by polarizing M2 macrophages.
Journal
Laboratory investigation; a journal of technical methods and pathology
ISSN: 1530-0307
Titre abrégé: Lab Invest
Pays: United States
ID NLM: 0376617
Informations de publication
Date de publication:
09 2019
09 2019
Historique:
received:
16
12
2018
accepted:
15
03
2019
revised:
11
03
2019
pubmed:
26
4
2019
medline:
1
7
2020
entrez:
26
4
2019
Statut:
ppublish
Résumé
Nonalcoholic steatohepatitis (NASH) is associated with lipotoxic liver injury, leading to insulin resistance, inflammation, and fibrosis. Despite its increased global incidence, very few promising treatments for NASH are available. Pirfenidone is an antifibrotic agent used to treat pulmonary fibrosis; it suppresses the pulmonary influx of T cells and macrophages. Here, we investigated the effect of pirfenidone in a mouse model of lipotoxicity-induced NASH via a high-cholesterol and high-fat diet. After 12 weeks of feeding, pirfenidone administration attenuated excessive hepatic lipid accumulation and peroxidation by reducing the expression of genes related to lipogenesis and fatty acid synthesis and enhancing the expression of those related to fatty acid oxidation. Flow cytometry indicated that pirfenidone reduced the number of total hepatic macrophages, particularly CD11c
Identifiants
pubmed: 31019294
doi: 10.1038/s41374-019-0255-4
pii: S0023-6837(22)02593-4
doi:
Substances chimiques
Protective Agents
0
Pyridones
0
pirfenidone
D7NLD2JX7U
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1335-1348Références
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