Estrogen receptor activation remodels TEAD1 gene expression to alleviate hepatic steatosis.

ABSTRACT: Sex-based differences in obesity-related hepatic malignancies suggest the protective roles of estrogen. Using a preclinical model, we dissected estrogen receptor (ER) isoform-driven molecular responses in high-fat diet (HFD)-induced liver diseases of male and female mice treated with or without an estrogen agonist by integrating liver multi-omics data. We found that selective ER activation recovers HFD-induced molecular and physiological liver phenotypes. HFD and systemic ER activation altered core liver pathways, beyond lipid metabolism, that are consistent between mice and primates. By including patient cohort data, we uncovered that ER-regulated enhancers govern central regulatory and metabolic genes with clinical significance in metabolic dysfunction-associated steatotic liver disease

SUBMITTER: Sommerauer C 

PROVIDER: S-EPMC10987545 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature