The N mice on the AIN-93M diet exhibited significantly increased hepatic iron contents (p < 0.05) and hepatic triglycerides (p < 0.05) compared with N mice fed the control diet. Splenic iron contents in N mice were significantly lower than those in J mice, even if control diets. The serum hep-cidin-25 to hepatic iron ratio was significantly higher in J mice compared with N mice on the AIN-93M diet. There were no differences in iron levels or fatty accumulation between J mice on the AIM-93M or control diet. The antioxidant status assessed by the ratio of BAP to dROM (p < 0.05) and microarray analysis revealed inhibition of p oxidation and mitochondrial complex IV. CPT1/2 expression levels

in mitochondria were significantly lower in N mice fed AIN-93M than in J mice fed AIN-93M. Finally, complex

IV function was significantly decreased selleck kinase inhibitor in N mice fed AIN-93M. In particular, the expression of the complex IV subunit (COX 7a2), which is thought to decrease due to the upregulation of methylation by aging and oxidative stress, was altered in N mice fed AIN-93M. Conclusions: The inhibition of COX 7a2 in mitochondrial complex IV might induce hepatic oxidative stress, fat accumulation, and iron metabolic disorder. Disclosures: The following people have nothing to disclose: Masaaki Korenaga, Mihoko Tsuji, Miyuki Kondo, Erina Kumagai, Misuzu Ueyama, Keiko Korenaga, Kazumoto Murata, Tatsuya Kanto, Naohiko Masaki, Masashi Mizokami Background and Aims:

Nonalcoholic fatty liver disease (NAFLD) is highly ABT-263 ic50 correlated to obesity and commonly found in developed countries. NAFLD is defined as excessive lipid accumulation in the liver, i.e., hepatosteatosis, characterized by elevated plasma levels of TG and LDL cholesterol, reduced HDL cholesterol and high blood pressure, and fasting hyper-glycemia. Targeting the liver can be challenging as most of the drugs available usually have significant side effects. As the main cells concerned with liver inflammation overexpressed CD98 during NAFLD, we aim here to investigate how a reduction/knock down of CD98 expression via CD98 siRNA loaded into nanoparticles Loperamide (NPs) can ameliorate the overall liver inflammation. Methods: NPs were made by double emulsion/solvent evaporation technique. To insure lysosomal escape and thus biological efficiency of the siRNA, we pre-complexed NPs with a small positive polymer called polyethylenimine (PEI). In vitro experiment have been performed on mice macrophages (MP) and human hepatic (HH) cells. Age and gender matched wild type (WT) mice were used for in vivo experiments to induce fatty liver by providing to mice 70% fat diet for 8 weeks. Mice were exposed to fat diet food for 8 weeks and received NPs loaded with CD98siRNA by intravenous injections twice a week. Control mice received scrambled siRNA loaded NPs along with fat diet.