Analysis of Neutral Lipid Accumulation and Lipotoxicity in Non-hepatocyte Liver Cells Under Free Fatty-acid Treatment

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) and its advanced form, nonalcoholic steatohepatitis (NASH), are prevalent diseases with no effective treatment available. NAFLD is marked by increased lipid accumulation in the hepatocytes, lobular inflammation fibrosis. However, effects of other hepatic lineage cells, such as endothelial cells (LEC), intrahepatic cholangiocytes (IHCHOLs), stellate (HSCs), on NAFLD/NASH progression less understood.
 METHODS: Human HSCs, IHCHOLs, LECs were isolated from explants healthy donors further characterized immunofluorescence staining. The treated different concentrations free acids (FFAs, oleic acid palmitic 2:1) for 48 hours, then examined staining BODIPY493/503. A cell viability assay LDH cytotoxicity performed. Real-time PCR was performed to monitor gene expression after treatment.
 RESULTS: Lipid confirmed BODIPY493/503 observed following treatment, especially higher FFA concentrations. No statistically significant difference or under FFA. a negative trend an increment dosage. upregulated genes LEC that related angiogenesis (CDH5), epithelial-mesenchymal transformation (TGF-β2 TGF-β3), cellular stress (P53), (IL-32) immunoglobular adhesion molecules (ICAM-1 VCAM-1) key monocyte response local inflammatory signal.
 CONCLUSION: Using vitro model system, we human types, LECs, dose-dependent treatment. This could be developed delineate adaptive responses within NAFLD/NASH.
 IMPACT: better understanding involvement hepatocytes lineages will augment development targeted treatments.