Fig. 7.

S217879 treatment induces a potent antioxidant response and inhibits a wide spectrum of pathways involved in MAFLD progression.

Human PCLS were generated from the liver of patients with MAFLD (n = 12) and treated with elafibranor (10 μM) or S217879 (3 μM) or vehicle (DMSO, 0.1%) for 2 days. (A) Heatmap of significantly differentially expressed genes from elafibranor and S217879-treated PCLS with MAFLD vs. vehicle-treated PCLS (adjusted p value cut-off <0.05). (B) Gene set-enrichment analysis of most differentially modulated pathways in elafibranor and S217879-treated PCLS with MAFLD vs. vehicle-treated PCLS. (C) Heatmaps and enrichment plots of differentially expressed genes in reactive oxygen species, (D) inflammatory response, and (E) extracellular matrix structural constituent pathways in elafibranor and S217879-treated PCLS vs. vehicle treated-PCLS. MAFLD, metabolic-associated fatty liver disease; NES, normalised enrichment score; PCLS, precision cut liver slices.