Chromatin remodeling in pericentral hepatocytes modulates MASH through CYP450 activity

The authors investigate how DPF2, a chromatin remodeling factor in Lgr5⁺ hepatocytes, regulates hepatic metabolism and contributes to the progression of metabolic liver diseases like MASLD and MASH. They demonstrate that loss of DPF2 leads to increased CYP2 enzyme activity, excessive metabolism of all-trans retinoic acid (atRA), and reduced AMPK phosphorylation, ultimately disrupting liver metabolic homeostasis. Their findings suggest that maintaining atRA levels could be a potential therapeutic strategy for managing these liver diseases.