Thus, in addition to lipoapoptosis, free fatty acids also activate a pro-inflammatory phenotype in cholangiocytes, suggesting a possible

role of cholangiocytes in inflammation and injury in non-alcoholic fatty liver disease. Disclosures: The following people have nothing to disclose: Mary A. Smith, Sathish Kumar Natarajan, Justin L. Mott Background/aims: Accumulating evidence supports that microRNAs (miRNAs) are important gene regulators, which can have critical roles in diverse cellular processes including non-alcoholic fatty liver disease (NAFLD). In the present study, we investigated the role of ABT-263 mw miR-451, which was identified as a target gene for NAFLD, in the mechanism of the inflammatory cytokine production in NAFLD. Methods: Microarray and stem-loop RT-PCR were performed PI3K Inhibitor Library to detect dysregulated miRNAs in a mouse model of high fat diet (HFD)-induced NAFLD. In addition, the direct miRNA targets were screened by pair-wise correlation coefficient analysis of the expressed mRNAs levels, and compared with predicted miRNA targets from TargetS-can5.1. To validate a candidate target gene, real time RT-PCR and Western blot

were performed in palmitate (PA)-exposed steatotic HepG2 cells transfected with control, miR-451 mimic or Cab39 siRNA. To determine whether AMP-activated protein kinase and NF-κB were downregulated, western blotting and luciferase reporter assays were performed in miR-451 mim-ic-transfected steatotic HepG2 cells. Results: We identified 7 new miRNAs-target gene pairs by bioinformatics analysis and further confirmed their expression by stem-loop RT-PCR (miR- 34a, miR-1224, miR-494, miR-455, miR-720, miR-451 and miR-19b) in a murine model of HFD-induced NAFLD. Among these genes, we found that miR-451 expression was down-regulated in non-alcoholic steatohepatitis (NASH).

We also found that Cab39/MO25 is the direct target of miRNA-451 in steatotic HepG2 cells. Mechanistically, we demonstrated that AMPK, activated through Cab39/MO25 as a direct target of miR-451, inhibits NF-κB transactivation induced by fatty acid PA in HepG2 cells. Consequently, overexpression of miRNA-451 in steatotic HepG2 cells suppressed PA-induced proinflammatory cytokine IL-8 expression. Conclusions: These results Thalidomide demonstrate the dysregulated miRNA/mRNA profiles in HFD-induced NAFLD in mice, and suggest that miRNA-451 may play an important role in the pathogenesis of NAFLD. This research was supported by grants of Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2012-001941). Disclosures: The following people have nothing to disclose: Wonhee Hur, Jung-Hee Kim, Joon Ho Lee, Sung Woo Hong, Seung Kew Yoon Background and Aim: Nonalcoholic steatohepatitis (NASH) is one of the major causes of liver disease, while two billion people are infected with hepatitis C virus (HCV) in the world.