Extended Data Fig. 9: Integration of the hepatic lipidome and transcriptome in mice overexpressing AGXT.
Male C57BL/6J mice were injected with AAV8-TBG-GFP or AAV8-TBG-AGXT (2x1011 viral genomes per mouse) and placed on the MASH diet for 24 weeks prior to end point analyses. a, Principal component analysis was performed based on untargeted lipidomics integrated with RNA-sequencing of livers from the same mice treated with AAV8-GFP or AAV8-AGXT (n=4). b, Heatmap of proinflammatory and lipotoxic sphingolipid metabolites (sphingomyelins, ceramides, and hexosylceramides) integrated with DEGs related to inflammatory and fibrotic pathways comparing livers from mice treated with AAV8-GFP or AAV8-AGXT (n=4, scale bar: relative abundance). Spearman’s correlations were calculated between the expression of proinflammatory/fibrotic genes and the abundance of (c) proinflammatory sphingolipid metabolites, and (d) PUFAs in triglycerides in livers from mice treated with AAV8-GFP or AAV8-AGXT. A p value <0.05 was considered statistically significant.
