Effects Of Omega-3 Fatty Acid On High-fat Diet-induced Liver Injury In C57BL/6J Mice

Objective:To investigate the protection of ω-3 Polyunsaturated Fatty Acids on metabolically triggered inflammation and liver damage from high-fat diet.Methods:70 male C57BL/6J mice were divided randomly into seven groups:Normal group (NG); High-fat diet group (HFD); ALA group (HFD+ALA); DHA group (HFD+DHA); DHA:EPA=2:1 group (HFD+DHA:EPA=2:1); DHA:EPA=1:1 group (HFD+DHA:EPA=1:1); DHA:EPA=1:2 group (HFD+DHA:EPA=1:2). Mice were pair-fed for 12 weeks until sacrificed after one overnight fasting. Serum was collected from blood. And then, serum AST and ALT were measured with kits based on enzymatic kinetic method. Liver tissue samples were fixed and tissue sections were stained with Hematoxylin-eosin staining (HE stain). The supernatants of liver homogenates with isopropanol were measured for the levels of hepatic TC, TG. Measurements of MDA, GSH and SOD were based on colorimetric assay. Serum TNF-α、IL-6 and IL-1β levels were measured using enzyme-linked immunosorbent assay kits. Real time-PCR was used to detect the gene expressions of TNF-α、IL-6、IL-1β、c-Jun and c-Fos in liver tissue samples. Immunohistochemistry and Western Blot were used to detect the protein levels of c-Jun and c-Fos in liver tissue samples.Results:1. Compared to normal control mice, HFD increased fatty infiltration in the liver by HE, accompanying with increased hepatic TC(P<0.01) and TG(P<0.01) contents and serum ALT(P<0.01) and AST(P<0.01) levels. The concentrations of TC, TG, ALT, AST and MDA of mice in all ω-3 PUFAs groups were significantly decreased compared with HFD group(P<0.01), and the concentrations of GSH and SOD in liver tissue samples were significantly increased(P<0.01). DHA was the most effective group in different ratios of ω-3 PUFAs to protect the liver oxidative damage.2. Compared with HFD group, the protein expressions of c-Jun and c-Fos were decreased in the hepatocyte nuclei in all ω-3 PUFAs groups, and the protein(P<0.05) mRNA(P<0.01) levels of c-Jun and c-Fos in liver tissue samples decreased significantly too. Compared with HFD group, serum TNF-a, IL-6, IL-1β of mice in all co-3 PUFAs groups were decreased (P<0.01), and hepatic mRNA levels decreased (P<0.05). DHA: EPA=1:2 group was the most effective group to protect liver inflammation induced by high-fat diet.Conclusion:co-3 Polyunsaturated Fatty Acids could protect the liver damage induced by high-fat diet through c-Jun and c-Fos of AP-1. For what has been discussed above, to the liver oxidative damage the most beneficial group is DHA group, and DHA:EPA=1:2 group was the most effective group to protect liver inflammation induced by high-fat diet.