Abstract
Nonalcoholic fatty liver disease (NAFLD) is one of the leading causes of chronic liver diseases. However, the pathogenesis of NAFLD is largely unknown. Here, we investigated the specific role of miR-499-5p in NAFLD. Free fatty acid was used to induce HL-7702 cell line to establish a NAFLD cell model, and animal models of NAFLD were constructed by feeding C57BL/6 mice with a high-fat diet. Expression levels of miR-499-5p in the HL-7702 cells and C57BL/6 mice were determined by quantitative real-time polymerase chain reaction. In addition, functional experiments were carried out through transfecting miR-499-5p inhibitor into NAFLD cells, and injecting NAFLD mice with a lentiviral vector with the miR-499-5p inhibitor. Furthermore, the effects of miR-499-5p on lipidation and inflammation were investigated by oil red O staining, hematoxylin-eosin staining, and biochemical analysis. Compared with normal controls, the expression of miR-499-5p was significantly up-regulated in NAFLD cells and tissues in mouse. After NAFLD cells transfected by miR-499-5p inhibitor, the expression of miR-499-5p was inhibited, the lipid deposition and content of triglycerides (TGs) were reduced, and the lipidation was improved. Simultaneously, after NAFLD mice were injected with the miR-499-5p lentiviral vector, the degree of lipid droplet deposition and content of TGs were also reduced. In addition, it decreased the levels of total cholesterol and aspartate aminotransferase in serum, and improved hepatic lipid metabolism. Inhibition of miR-499-5p expression improved NAFLD in mice, which provided a new direction for the treatment of NAFLD.
Highlights
Nonalcoholic fatty liver disease (NAFLD) is one of the leading causes of chronic liver diseases
The results indicated that the NAFLD cell model was successfully established by culturing with Free fatty acid (FFA) high fat culture medium for 24 h
In high fat diet (HFD) group, diffuse hepatic steatosis was occurred in the liver of mice, which showed microvesicular steatosis, and no obvious inflammatory cell infiltration, hepatocyte necrosis and fibrosis (Figure 2B)
Summary
Nonalcoholic fatty liver disease (NAFLD) is one of the leading causes of chronic liver diseases. Non-alcoholic fatty liver disease (NAFLD) is a disease associated with abnormal lipid accumulation in hepatocytes, which might develop into fibrosis, cirrhosis and even canceration under certain circumstances [1, 2]. Steatosis (accumulation of fat droplets in hepatocytes), inflammation, balloon damage, fibrosis and cirrhosis are the pathological features of NAFLD [3]. Causes of NAFLD mainly include changes in fat metabolism, proinflammatory and anti-inflammatory molecular imbalances [4]. NAFLD is a liver manifestation of metabolic and inflammatory liver disease, a high fat (HF) diet triggers steatosis and induces lipotoxicity, inflammation and insulin resistance [7]. With the widespread outbreak of NAFLD, molecular targeting technology has become a hot spot for the treatment of this disease
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