Sex-specific KDM6A-HNF4A-CREBH network controls lipoprotein cholesterol metabolism and atherosclerosis via epigenetic reprograming of hepatocytes - PubMed
6 hours ago
- #atherosclerosis
- #KDM6A
- #cholesterol metabolism
- The liver plays a central role in lipid and cholesterol metabolism, influencing lipoprotein profiles and cardiovascular disease risk.
- Sex-specific differences exist in cholesterol handling and atherosclerosis susceptibility, with molecular mechanisms not fully understood.
- The X-linked histone demethylase KDM6A is crucial for maintaining healthy cholesterol metabolism in the liver.
- Reducing KDM6A levels in female human liver cells disrupts lipoprotein regulation gene programs linked to cardiovascular disorders.
- Female mice lacking KDM6A in hepatocytes develop pro-atherogenic lipoprotein profiles and increased atherosclerosis, while males are unaffected.
- KDM6A collaborates with HNF4A to activate chromatin and enable CREBH-dependent transcription of lipid metabolic genes.
- The study identifies KDM6A as a sex-linked regulator of hepatic cholesterol metabolism.