Inflammatory stress aggravating CCl4-induced hepatic lipid accumulation in the mice via SREBP-1-HMGCR pathway

Abstract:

Objective：To investigate whether inflammatory stress aggravates hepatosteatosis induced by carbon tetrachloride（CCl4） and the molecular mechanism. Methods：Male C57BL/6J mice of 6-8 weeks were randomly divided into control group（n=6） and inflam－mation group（n=6）. Inflammation was induced via subcutaneous casein injection of casein for 16 weeks after the treatment of CCl4 for 2 weeks. After 18 weeks，the liver indicator was measured to study the damage to the liver. Level of serum inflammatory factor inter－leukin-6（IL-6） was determined by ELISA. Oil red O staining was used to evaluate lipid accumulation in the liver. Lipid levels of liver tissues were measured by chemical enzymatic assay. mRNA expression of SREBP-1 and 3-hydroxy-3-methylglutaryl coenzyme A re－ductase（HMGCR） was measured by real-time PCR and the protein expression of SREBP-1 and HMGCR was analyzed by Western blot. Results：Expression of IL-6 was higher in inflammation group than in control group（t=8.434，P=0.000）. Expression of HMGCR and SREBP-1 mRNA was significantly increased in inflammation group than in control group（t=10.612，P=0.000；t=12.749，P=0.000）. Expressions of SREBP-1 and HMGCR protein were consistent with the mRNA levels based on Western blot. Hepatic lipid levels were significantly higher in inflammation group than in control group（t=6.148，P=0.000；t=7.288，P=0.000）. Liver indicator of mice were significantly higher in inflammation group than in control group（t=8.452，P=0.000）. Increased lipid accumulation demonstrated by Oil red O staining was observed in inflammation group. Conclusion：Inflammatory stress probably promotes cholesterol synthesis in fatty liver induced by CCl4 via SREBP-1-HMGCR pathway，which may contribute to the abnormal lipid accumulation in the liver.