CD98 siRNA-loaded nanoparticles decrease hepatic steatosis in mice

Brandon S B Canup; Heliang Song; Vu Le Ngo; Xiangxiao Meng; Timothy L Denning; Pallavi Garg; Hamed Laroui

doi:10.1016/j.dld.2016.11.008

CD98 siRNA-loaded nanoparticles decrease hepatic steatosis in mice

Dig Liver Dis. 2017 Feb;49(2):188-196. doi: 10.1016/j.dld.2016.11.008. Epub 2016 Nov 17.

Authors

Brandon S B Canup¹, Heliang Song¹, Vu Le Ngo², Xiangxiao Meng¹, Timothy L Denning², Pallavi Garg², Hamed Laroui³

Affiliations

¹ Department of Chemistry, Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA, USA.
² Department of Biology, Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA, USA.
³ Department of Chemistry, Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA, USA; Department of Biology, Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA, USA. Electronic address: [email protected].

Abstract

Non-alcoholic fatty liver disease (NAFLD) is characterized by excessive lipid hepatic accumulation. Here, we investigated whether a reduction of CD98 expression mediated by CD98 siRNA-loaded nanoparticles (NPs) could attenuate liver disease markers in a mouse model of NAFLD. NPs were generated using a double emulsion/solvent evaporation technique. Mice fed a high fat diet for 8 weeks to induce fatty liver were treated with vein tail injections of CD98 siRNA-loaded NPs. In vitro, HepG2 treated with CD98 siRNA-loaded NPs showed significant downregulation of CD98 leading to a significant decrease of major pro-inflammatory cytokines and markers. In vivo, CD98 siRNA-loaded NPs strongly decreased all markers of NAFLD, including the blood levels of ALT and lipids accumulation, fibrosis evidence and pro-inflammatory cytokines. In conclusion, our results indicate that CD98 appears to function as a key actor/inducer in NAFLD, and that our NPs approach may offer a new targeted therapeutic for this disease.

Keywords: Hepatic CD98; Nonalcoholic fatty liver; Targeted therapeutic strategy; siRNA-loaded nanoparticles.

MeSH terms

Animals
Biomarkers / blood
Diet, High-Fat
Disease Models, Animal
Down-Regulation
Female
Fusion Regulatory Protein-1 / genetics*
Gene Silencing*
Humans
Mice
Nanoparticles / chemistry
Non-alcoholic Fatty Liver Disease / therapy*
RNA, Small Interfering / genetics*

Substances

Biomarkers
Fusion Regulatory Protein-1
RNA, Small Interfering

Grants and funding

K01 DK097192/DK/NIDDK NIH HHS/United States