Hamed Laroui, Brandon S B Canup, Jenniffer L M Stetler, Qiang Ma, Russell P Pucket, Brandon K Hodges and Pallavi Garg
Accepted Abstracts: J Nanomed Nanotechnol
Nonalcoholic fatty liver disease is highly correlated to obesity and thus commonly found in developed countries. It is defined as excessive lipid accumulation in the liver, i.e., hepatosteatosis. Nanotechnology, including nanoparticles (NPs), for drug delivery system is an alternative solution to prevent cytotoxicity of drugs. As the main cells concerned with liver inflammation overexpressed CD98 during NAFLD, the aim here is to investigate how a reduction/knock down of CD98 expression via CD98 siRNA loaded into NPs can ameliorate the overall liver inflammation. After accessing in vitro on mice macrophages and human hepatic cells that CD98 siRNA NPs significantly reduced CD98 expression, the study in mice model of fatty liver disease was translated. 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. Liver, spleen, colon and main organs were collected to respectively analyze overexpression of cytokines and fatty liver markers, mRNA level, and perform histology (H&E and Oil red to stain cytosolic lipid vacuoles inclusions). 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 was all attenuated in significant proportion when mice received CD98 siRNA loaded NPs. Together, the data show that diminution of expression 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.
Hamed Laroui has completed his PhD in 2007 from Henri Poincare and Polytechnics University (France) and Postdoctoral studies from Emory University School of Medicine (Gastroenterology division). He is now Assistant Professor at Georgia State University serving as Director of the Biophysical Group. He has published more than 29 papers in reputed journals and serving as reviewer for reputed journals such as Gastroenterology, Molecular therapy, JBC.