Sex differences in Non-Alcoholic Steatohepatitis (NASH) in mice evoked by a fructose-palmitate-cholesterol (FPC)-enriched diet [single_nucleus]

To study sex differences in the response to NASH in mice, single nucleus RNA sequencing of livers was performed. Single nucleus RNAseq demonstrated enrichment of differentially-expressed genes particularly in hepatocytes and stellate cells in females versus males fed FPC-NASH. Multiple regulons (transcription factors and target genes) implicated in lipid and other metabolic processes and hormone signaling (hepatocytes) and cell-cell communication and cell adhesion (stellate cells) were noted, which were enriched in female versus male FPC-NASH diet. Bulk liver RNAseq and RNAseq of isolated hepatocytes and hepatic stellate cells were analyzed as validation experiments. Overall design: Male and female C57BL/6J mice were fed fructose-palmitate-cholesterol (FPC-NASH) diet or standard chow (SC) for 16 weeks. Single-nucleus RNAseq was performed on the top left lobe of livers from control and FPC diet fed male and female mice (N = 2 independent mice/group, resulting in 8 samples total). Samples from each of the 2 replicate groups were hashtagged and sequenced as one pool.