Results: NPs have a size that can be controlled (D=400 nm) and increase the rate of siRNA loaded into the NPs (15.2 μg/ mg of NPs with PEI versus 4.2 μg/mg of NPs without PEI). In vitro, we showed on MP and HH that CD98 siRNA NPs significantly reduced CD98 expression. Thus, we translated our study in mice model of fatty liver diseases. In vivo, mice receiving NPs loaded with CD98siRNA have significantly reduced signs of liver inflammation and lipid accumulation. In addition, Evidence of hepatic injury such

as hepatocyte ballooning, increased blood levels of ALT, hepatic inflammation, oxidative stress were all attenuated in significant proportion when mice received CD98 siRNA loaded NPs. Conclusion: Together, the data show that diminution Daporinad nmr of expression Hydroxychloroquine chemical structure of CD98 in hepatic cells strongly correlated with a diminution of NAFLD signs thereby CD98 seems to act like as a steatosis actor/ inducer in NAFLD. This study also proposes a novel treatment of NAFLD using

nanosized vehicles loaded with siRNA, which may provide a new therapeutic approaches in liver diseases. Disclosures: The following people have nothing to disclose: Jenniffer L. Stetler, Brandon S. Canup, Qiang Ma, Russell P. Pucket, Hamed Laroui [Background] We have been focusing on lipid droplets (LDs) and reported that ubiquitinated Apolipoprotein B (ApoB) accumulates in hepatocyte LDs when proteasome or autophagy is downregulated. We also found that UBXD8 is a key molecule for degradation of lipidated ApoB around LDs. To address the function of UBXD8 in liver in vivo, we generated hepato-cyte-specific UBXD8 knockout (KO) mouse and examined the phenotype in detail. [Method] Mice with the floxed exon1

of the UBXD8 locus were generated and crossed with mice expressing the albumin promoter-driven Cre recombinase MCE to generate hepatocyte-specific UBXD8-KO mice. KO mice and their age-matched littermates (WT) were fed either a normal diet (4.6% fat) or a high-fat diet (14.4% fat) for 26 weeks starting at 4 weeks old. [Results] (1) At 16 weeks old (12 weeks after starting the aforementioned feeding), no significant difference was observed between WT and KO mice on the normal diet feeding. (2) After 26 weeks of the high-fat diet feeding, 50% (15/30) of WT mice showed macrovesicular steatosis primarily in the perivenular area (zone 3), whereas 56% (17/30) of KO mice showed macrovesicular steatosis mainly in the periportal area (zone 1). (3) The serum triglyceride (TG) level in KO mice on the high-fat diet was significantly lower than WT mice on the high-fat diet (44 mg/dl vs. 65 mg/dl, P=0.001). By HPLC analysis of serum lipoproteins, TG in VLDL was revealed to decrease prominently in KO mice fed the high-fat diet.