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

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, RNAseq of isolated hepatocytes and hepatic stellate cells, and spatial transcriptomics, were analyzed as validation experiments. Spatial transcriptomics was performed on the top left lobe of livers from FPC-NASH diet fed male mice.