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Liver Endothelial Zonation Orchestrates Hepatic Steatosis Onset through Retinoic Acid-regulated FGF1

GSE315455 Mus musculus Expression profiling by high throughput sequencing 8 samples Submitted 2026/05/05 Platform GPL24247
Summary
The contribution of liver sinusoidal endothelial cell (LSEC) zonation to metabolic dysfunction-associated steatotic liver disease (MASLD) pathogenesis remains undefined. We identified selective lipid deposition in the pericentral zone during early MASLD. Multi-omics analyses confirmed enhanced pericentral lipid metabolism in both hepatocytes and LSECs. Mechanistically, pericentral LSEC marker c-Kit transcriptionally activated FGF1 via nuclear receptor RXRG, which suppressed hepatocellular lipid accumulation through FGFR4 signaling. Remarkably, retinoic acid (RXRG’s endogenous ligand and active vitamin A metabolite) phenocopied FGF1’s anti-steatotic effects. Clinical data revealed an inverse correlation between dietary vitamin A and MASLD severity, suggesting therapeutic potential of vitamin A supplementation for early intervention.
Published in
Liver endothelial zonation orchestrates hepatic steatosis onset through retinoic acid-regulated FGF1
Fang Z, Che B, Ling Y et al. · Science advances 2026 · PMID 42319926 · doi:10.1126/sciadv.aed4384
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Also filed as BioProject PRJNA1397179 and SRA study SRP659369. Searching any of these in the dataset finder brings you back here.

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