Genome-wide liver transcriptomic profiles from chow-fed, high fat diet (HFD) fed, and HFD + AC261066 (Retinoic Acid Receptor Beta-2 Selective Agonist) fed mice

Using a high fat diet (HFD) mouse model of nonalcoholic fatty liver disease (NAFLD) with 60% of the energy derived from fat, we determined the effects of AC261066, a RARbeta2 selective agonist, on the liver transcriptome. We analyzed disease signature pathways using our genome-wide RNA-seq data from AC260166 treated livers and show that AC261066 limits the mRNA increases of NAFLD driver genes PKLR, FASN, THRSP, and CHCHD6. Moreover, AC261066's effects on the hepatic stellate cell (HSC) secretome signature and changes in other transcripts that contribute to fibrosis suggest that AC261066 suppresses the initiation of liver fibrosis, which characterizes NASH. Our RNA-seq data also indicate an anti-inflammatory effect of AC261066. In conclusion, based on our genome-wide analysis of the transcriptome of NAFLD, we suggest that AC261066 has potential therapeutic relevance for the prevention/treatment of NAFLD and NASH. Overall design: Examination of genome-wide transcript levels in mouse liver samples.