Visfatin exacerbates hepatic inflammation and fibrosis in a methionine-choline-deficient diet mouse model.
J Gastroenterol Hepatol
; 36(9): 2592-2600, 2021 Sep.
Article
em En
| MEDLINE
| ID: mdl-33600604
ABSTRACT
BACKGROUND AND AIM:
Non-alcoholic fatty liver disease (NAFLD) ranges from simple steatosis to non-alcoholic steatohepatitis, which is characterized by hepatic inflammation that can progress to fibrosis, cirrhosis, and hepatocellular carcinoma. Visfatin, an adipocytokine, was reported to induce pro-inflammatory cytokines and can be associated with liver fibrosis. We investigated the role of visfatin on hepatic inflammation and fibrosis in a methionine-choline-deficient (MCD)-diet-induced steatohepatitis mouse model.METHODS:
Eight-week-old male C57BL/6 J mice were randomly assigned into one of three groups (1) saline-injected control diet group; (2) saline-injected MCD diet group; and (3) visfatin-injected MCD diet group (n = 8 per group). Mice were administered intravenous saline or 10 µg/kg of recombinant murine visfatin for 2 weeks. Histologic assessment of liver and biochemical and molecular measurements of endoplasmic reticulum (ER) stress, reactive oxidative stress (ROS), inflammation, and fibrosis were performed in livers from these animals.RESULTS:
Visfatin injection aggravated hepatic steatosis and increased plasma alanine aminotransferase and aspartate aminotransferase concentrations. Visfatin increased inflammatory cell infiltration (as indicated by F4/80, CD68, ly6G, and CD3 mRNA expression) and expression of chemokines in the liver. Visfatin also increased the expression of pro-inflammatory cytokines (IL-1ß, TNF-α, and IL-6) and activated fibrosis markers (CTGF, TIMP1, collagen 1α2, collagen 3α2, αSMA, fibronectin, and vimentin) in liver. Livers of visfatin-injected mice showed upregulation of ER stress and ROS and activation of JNK signaling.CONCLUSIONS:
These results suggest that visfatin aggravates hepatic inflammation together with induction of ER and oxidative stress and exacerbates fibrosis in an MCD-diet-fed mouse model of NAFLD.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Dieta
/
Adipocinas
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Nicotinamida Fosforribosiltransferase
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Doença Hepática Induzida por Substâncias e Drogas
/
Hepatopatia Gordurosa não Alcoólica
Tipo de estudo:
Etiology_studies
/
Evaluation_studies
/
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article