The ULK1-NCOA3 axis restrains de novo lipogenesis and prevents diet-induced steatohepatitis and fibrosis in mice - PubMed
19 hours ago
- #NCOA3
- #Lipogenesis
- #ULK1
- ULK1 is significantly repressed in human MASH livers.
- Hepatocyte-specific ULK1 loss promotes hepatic steatosis and liver fibrosis without affecting basal autophagy flux.
- Phospho-proteomics identified NCOA3 as a downstream phospho-target of ULK1.
- ULK1 phosphorylates NCOA3 to repress its transcriptional activity and restrain CREB/CBP-mediated de novo lipogenesis.
- A phosphorylation-deficient NCOA3 mutant drives lipogenesis, while NCOA3 inhibition prevents steatosis, inflammation, and profibrotic signaling.
- The ULK1-NCOA3 axis is a druggable checkpoint against the entire MASLD spectrum.