Liver Stiffness Directs Intrahepatic Cholesterol Accumulation Through YAP/TAZ in Metabolic Dysfunction-Associated Steatotic Liver Disease - PubMed
6 hours ago
- #Liver Stiffness
- #Cholesterol Metabolism
- #MASLD
- Elevated liver stiffness is linked to morbidity and mortality in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD).
- Liver stiffness influences intrahepatic cholesterol levels, with a strong correlation observed in both human MASLD cohorts and mouse models.
- Stiff matrices promote spontaneous cholesterol accumulation in hepatocytes by mechanosensitively repressing Liver X receptor alpha (LXRα).
- Yes-associated protein (YAP) and Transcriptional coactivator with PDZ-binding motif (TAZ) activation repress LXRα activity, disrupting its heterodimerization with Retinoid X receptor alpha (RXRα).
- Hepatocyte-specific ablation of Yap/Taz enhances hepatic cholesterol efflux and delays cholesterol-induced fibrosis progression in mice.
- Transcriptomic analysis of MASLD patient livers shows an inverse correlation between LXRα target gene expression and liver stiffness/YAP/TAZ activity.
- The findings suggest liver stiffness as a causal factor for hepatocyte dysfunction in MASLD.