RNAseq of liver dendritic cells targeted with empty liposomes or curcumin liposomes

Non-alcoholic fatty liver disease (NAFLD) is a common complication of obesity, where insulin resistance and hepatocyte fat deposition may progress to steatohepatitis (NASH) and fibrosis/ cirrhosis. NASH has no approved treatment. Consequent upon hepatic fat deposition, NF-κB activation in hepatic myeloid cells mediates inflammation and NASH progression. We delivered micro-doses of liposome-encapsulated lipophilic NF-κB inhibitors, curcumin or 1,25-dihydroxy-vitamin D3 (calcitriol), to the pro-fibrogenic inflammatory liver macrophages and dendritic cells (DCs) in diet-induced NASH. After i.v. administration, liver was the primary organ targeted. MHC class-II+ hepatic DCs taking up liposomes in mice and human were F4/80+ and CD14+ respectively, were lipid-laden and expressed pro-inflammatory genes. Curcumin or calcitriol liposomes suppressed hepatic inflammation, fibrosis and fat accumulation, and reduced insulin resistance associated with suppression of immune activation, cell cycle and collagen deposition pathways in vivo. Thus, hepatic inflammatory DCs passively targeted with liposomes encapsulating lipophilic NF-κB inhibitors are beneficial in NASH. Female C57BL/6 mice were fed with methioinine and choline deficient diet for 2 weeks to induce nonalcoholic steatohepatitis. Groups of mice were intravenously injected with either DiI labelled empty liposomes or DiI labelled curcumin liposomes. 24 hours later hepatic dendritic cells (CD11c+MHC class-II+) that are either positive or negative for DiI were FACS sort purified to compare the transcriptome profiling.