• FTO is upregulated during HSC activation and BDL-induced hepatic fibrosis, promoting autophagy and fibrosis progression.
• FTO directly demethylates ULK1 mRNA at m6A sites, increasing ULK1 expression and driving autophagic activation of HSCs.
• YTHDC2 acts as a negative regulator by binding to m6A-modified ULK1 mRNA, reducing its stability and inhibiting autophagy.
• Targeting the FTO/ULK1/YTHDC2 axis offers a novel therapeutic strategy for cholestatic liver fibrosis.