Visfatin exacerbates hepatic inflammation and fibrosis in a methionine-choline-deficient diet mouse model.

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-1β, 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.

• Authors: Yu Jung Heo, Sung-E Choi, Nami Lee, Ja Young Jeon, Seung Jin Han, Dae Jung Kim, Yup Kang, Kwan Woo Lee, Hae Jin Kim
• Journal: Journal of gastroenterology and hepatology (J Gastroenterol Hepatol) Vol. 36 Issue 9 Pg. 2592-2600 (Sep 2021) ISSN: 1440-1746 [Electronic] Australia
• PMID: 33600604 (Publication Type: Evaluation Study, Journal Article)
• Copyright: © 2021 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Chemical References

• Adipokines
• Methionine
• Nicotinamide Phosphoribosyltransferase

Topics

• Adipokines (adverse effects)
• Animals
• Chemical and Drug Induced Liver Injury (etiology, immunology, pathology)
• Choline Deficiency (complications)
• Diet (adverse effects)
• Disease Models, Animal
• Inflammation (chemically induced, immunology, pathology)
• Liver (immunology, pathology)
• Liver Cirrhosis (chemically induced, immunology, pathology)
• Male
• Methionine (deficiency)
• Mice
• Mice, Inbred C57BL
• Nicotinamide Phosphoribosyltransferase (adverse effects)
• Non-alcoholic Fatty Liver Disease (etiology, pathology)