Chromatin remodeling in pericentral hepatocytes modulates MASH through CYP450 activity - PubMed
6 hours ago
- #Hepatocyte Regulation
- #Chromatin Remodeling
- #Metabolic Liver Disease
- Lgr5+ hepatocytes are specialized cells involved in nutrient and xenobiotic metabolism, and DPF2 in these cells is essential for metabolic homeostasis.
- Loss of Dpf2 in Lgr5+ hepatocytes leads to severe MASLD by increasing CYP2 enzyme expression, which excessively metabolizes all-trans retinoic acid (atRA), reducing AMPK phosphorylation.
- Restoration of atRA rescues AMPK activity and reduces MASLD severity, revealing a non-cell-autonomous mechanism linking these hepatocytes to whole-liver regulation.
- DPF2 acts via the CYP2-atRA-AMPK axis, making atRA homeostasis a potential therapeutic target for MASLD and MASH.
- The findings highlight that chromatin regulation in spatially restricted cell populations can drive liver-wide metabolic reprogramming, suggesting targeted therapies.