Abstract
Non-alcoholic fatty liver disease (NAFLD) causes liver dysfunction and is associated with obesity and type 2 diabetes. Chronic inflammation is associated not only with the development of NAFLD, but also with hepatic diseases, including steatohepatitis, cirrhosis, and hepatocellular carcinoma. Auranofin is a treatment for rheumatoid arthritis and has recently been reported to have potential effects against a variety of diseases, including inflammation, cancer, and viral infection. In this study, auranofin may be considered as a new treatment for the management of metabolic syndrome, as well as in the treatment of NAFLD through immunomodulation. To determine the effect of auranofin on NAFLD, C57BL/6 mice were randomly grouped, fed a regular diet or a high fat diet (HFD), and injected with normal saline or auranofin for 8 weeks. Auranofin significantly decreased the body weight, epididymal fat weight, serum aspartate aminotransferase (AST), and glucose, as well as the serum triglyceride, cholesterol, and low-density lipoprotein cholesterol levels as compared to the HFD group. We also observed that hepatic steatosis was increased in the HFD group and was suppressed by auranofin treatment. In addition, auranofin suppressed the expressions of interleukin (IL)-1β, IL-18, caspase-1, and the NOD-like receptor family pyrin domain containing 3 (NLRP3) in the liver tissue. Furthermore, the expression of NADPH oxidase 4 and peroxisome proliferator-activated receptor γ (PPARγ), which are a major source of oxidative stress and a regulator of adipogenesis, respectively, were also decreased by auranofin. In addition, primary mouse hepatocytes were incubated with lipopolysaccharide (LPS) and palmitic acid (PA) to induce lipid accumulation and hepatic inflammation for an in vitro model. Auranofin could significantly inhibit LPS- and PA-induced inflammatory activity including nitric oxide and NLRP3 inflammasome-mediated cytokines. The results of this study demonstrate that auranofin treatment inhibits the characteristics of NAFLD through the inhibition of NLRP3 inflammasome. Therefore, auranofin may have potential as a candidate for improving NAFLD symptoms.
Highlights
Non-alcoholic fatty liver disease (NAFLD) is a metabolic disease caused by the excessive storage of fat in the liver, not liver disease caused by other causes such as alcohol, drugs and virus [1,2]
The NAFLD process develops into nonalcoholic steatohepatitis (NASH) by lipid accumulation in hepatocytes, which causes reactive oxygen species, lipid peroxidation, and proinflammatory cytokines leading to hepatic injury and inflammation [7,8]
The whole-body size and weight of the high fat diet (HFD) group increased as compared to the control group (Figure 1A–C)
Summary
Non-alcoholic fatty liver disease (NAFLD) is a metabolic disease caused by the excessive storage of fat in the liver, not liver disease caused by other causes such as alcohol, drugs and virus [1,2]. It is reported that NAFLD increases exacerbated chronic inflammation and oxidative stress, causing dysfunction in liver tissues. The NAFLD process develops into nonalcoholic steatohepatitis (NASH) by lipid accumulation in hepatocytes, which causes reactive oxygen species, lipid peroxidation, and proinflammatory cytokines leading to hepatic injury and inflammation [7,8]. NAFLD can advance into steatohepatitis, fibrosis and cirrhosis, and hepatocellular carcinoma [9,10]. NAFLD, which has the ability to develop from metabolic syndrome to steatohepatitis and hepatocellular carcinoma, requires an effective treatment [11,12]. It is important to understand how NAFLD progresses so we can develop an effective treatment
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