Abstract
Objective To investigate the effects of ribosomal protein S6 kinase 1 (S6K1) gene silencing on the pathogenesis of non-alcoholic fatty liver disease. Methods Twelve 9-week male db/db mice (body weight 44.5 to 48.2 g)were randomly assigned to the normal control group(n=6) and the study group(n=6). The mice in the study group were injected with S6K1 short hairpin RNA recombinant adenovirus (S6K1Ax) via the tail vein, and the control group was given U6 promoter recombinant adenovirus (pU6Ax). Six days after virus injection, db/db mice were killed and livers were harvested. Hepatic protein expression of insulin receptor substrate 1(IRS1), insulin receptor substrate 2(IRS2) and protein kinease B(Akt), Akt473 was determined by Western blot in the two groups. Total hepatic RNAs were extracted to analyze genes expression of fatty acids synthesis by using real-time quantitative reverse transcription polymerase chain reaction. Blood was collected after 16 h of fasting before db/db mice were killed. The serum free fatty acids, triglyceride and cholesterol levels were quantified by colorimetry. The data of the two groups were compared with t-test. Results Six days after virus injection, fat droplet in hepatocyte decreased in study group compared with that in control group under HE staining observation and the fatty liver in study group was improved. Protein expression of S6K1 in the study group was down-regulated significantly compared with that in control group (0.12±0.01 vs 0.87±0.06, t=5.36, P 0.05). Conclusions Given excess nutrient, over-activated hepatic ribosomal protein S6 kinase 1 maybe cause hepatic insulin resistance and fatty liver through negative feedback and up-regulating SREBP1c expression. Key words: Fatty liver; Mice; Ribosomal protein S6 kinases, 70-kDa; Gene silencing; Insulin resistance
Published Version
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