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. Overall design: Spatial transcriptomics was performed on the top left lobe of livers from FPC-NASH diet fed male mice.