Loss of PPARα function promotes epigenetic dysregulation of lipid homeostasis driving ferroptosis and pyroptosis lipotoxicity in metabolic dysfunction associated Steatotic liver disease (MASLD).

Remarkably, TRRUST motif analysis of hypermethylated genes in PPARα KO mice shows highly significant enrichment of PPRE ( Figure 5C ), which is still significantly enriched in WT CDAHFD mice which only partially express PPARα protein ( Figure 5D ).

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