Visfatin exacerbates hepatic inflammation and fibrosis in a methionine‐choline‐deficient diet mouse model. Issue 9 (28th February 2021)

• Record Type: Journal Article
• Authors: Heo, Yu Jung; Choi, Sung‐E; Lee, Nami; Jeon, Ja Young; Han, Seung Jin; Kim, Dae Jung; Kang, Yup; Lee, Kwan Woo; Kim, Hae Jin
• Is Part Of: Journal of gastroenterology and hepatology. Volume 36:Issue 9(2021)
• Page Start: 2592
• Page End: 2600
• Publication Date: 2021-02-28
• Subjects: hepatic fibrosis -- hepatic inflammation -- methionine‐choline‐deficient diet -- visfatin; Gastroenterology -- Periodicals; Digestive organs -- Diseases -- Periodicals; Liver -- Diseases -- Periodicals; Gastroenterology -- Periodicals; Liver Diseases -- Periodicals; 616.33
• DOI: 10.1111/jgh.15465
• Languages: English
• ISSNs: 0815-9319

Abstract

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.